Dissertations / Theses on the topic 'Oxidative stress factors'
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1
Wong, Hoi-kin, and 黃凱健. "New factors that affect adrenomedullin expression." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/195971.
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ADM is a 52-amino acid peptide which carries out multiple biological functions in cardiovascular system such as vasodilation and hypotension, and is a prognostic marker for cardiovascular diseases. Recent studies show that its plasma level is elevated in diabetes, however the reason and significance for such an increase has not been understood. Recent research has proposed that inflammation and oxidative stress both contribute to the pathogenesis of diabetes. If ADM is a marker in diabetes, it is possible that ADM is regulated by these two mechanisms, and so this project aims to investigate how these mechanisms could affect ADM expression.
Recent studies have demonstrated that advanced glycation endproducts (AGEs) could lead to development of various diabetic complications. AGEs are formed as intermediate product in the non-enzymatic glycation of reducing sugars. Formation of these products is stimulated by hyperglycemia and oxidative stress, which could also induce ADM expression. Hence one of the studies investigated the direct effect of AGEs on ADM expression in an in vitro model. A rat macrophage cell line NR8383 was used to investigate the dose-response and time-point responses of macrophage cells in expressing ADM stimulated by AGEs. 6 hours of AGEs treatment resulted in no significant effect on ADM gene expression. The gene expression increased in all time points in which the change was at maximum after 1 hour of AGE treatment compared with other time points (P<0.05). However the time-dependent effect on ADM gene expression was insignificant compared with controls. How oxidative stress could lead to increased ADM expression deserves further investigation.
ADM plays a role in inflammation that it could influence IL-6 and adiponectin expressions. This project also investigated whether IL-6 and adiponectin could affect ADM levels on the opposite. The associations between IL6 and adiponectin single nucleotide polymorphisms (SNPs) with plasma ADM levels were studied using a cohort of 476 subjects from the Cardiovascular Risk Factor Prevalence Study (CRISPS). Specific tagging SNPs were genotyped for the 476 subjects. Significant associations were identified for the IL6 SNP rs17147230 and adiponectin SNP rs182052 with plasma ADM levels in additive model (β=-0.096, P=0.034, and β=0.104, P=0.023 respectively adjusting for age and sex). The associations remained significant after adjusting for various covariates (P<0.05). Genotypic model shows that the minor alleles of rs17147230 and rs182052 resulted in 12.8% decrease and 17.7% increase in plasma ADM levels. These findings show that ADM level could be regulated by IL-6 which is an inflammatory cytokine, and adiponectin which is a protective peptide in inflammation. Reducing inflammation could lower ADM level and adiponectin might be a therapeutic candidate.published_or_final_version
Medicine
Master
Master of Philosophy
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Goumenaki, Eleni. "Factors governing the sensitivity of lettuce to ozone-induced oxidative stress." Thesis, University of Newcastle Upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432760.
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Poljak, Anne Medical Sciences Faculty of Medicine UNSW. "Oxidative, inflammatory and vascular factors in Alzheimer's disease." Publisher:University of New South Wales. Medical Sciences, 2008. http://handle.unsw.edu.au/1959.4/41273.
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In spite of impressive recent progress, the aetiopathogenesis of Alzheimers disease (AD) remains incompletely understood. The distinctive neuropathological features of AD, in particular the plaques and tangles, have been the particular focus of most aetiological theories. It is well accepted that AD is a multifactorial disease, with alterations to a variety of brain structures and cell types, including neurons, glia and the brain vasculature. Studies of risk factors have revealed a diversity of genetic variables that interact with health, diet and lifestyle-related factors in the causation of AD. These factors influence the structure, aggregation and function of a set of proteins that are increasingly the focus of research. The work in this thesis has focused on the pathophysiological aspects of some of these proteins in a number of cellular compartments and brain. Several assays have been established and techniques utilized in the completion of this work, including; differential detergent fractionation of brain tissue, 1D and 2D PAGE, western blotting with chemiluminescence detection, ELISA assays of Abeta 1-40 and 1-42, quantitative ECNI GCMS of o- and m-tyrosine as well as metabolites of the kynurenine pathway, quantitative MALDI-TOF assay of hemorphins and LCMSMS based proteomics, to identify proteins with altered expression levels in AD relative to control brain tissue. A variety of regional differences have been observed in the biochemistry of the AD cortex which are probably the outcome of local response variations to AD pathology. One of the most consistent threads throughout this work has been an apparent resilience of the occipital lobe relative to the other brain regions, as reflected in lower overall levels of oxidative stress and increased levels of proteins associated with metabolic processes, neuronal remodeling and stress reduction.
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Yuan, Jianfeng. "Effects of hyperbaric oxygen on oxidative stress, angiogenesis factors and endothelial cell injury." Thesis, University of Plymouth, 2007. http://hdl.handle.net/10026.1/2451.
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Hyperbaric oxygen (HBO) therapy is the administration of 100% oxygen at more than one atmosphere. It greatly improves tissue oxygenation and facilitates mechanisms of wound healing, which in turn benefits some patients with chronic wounds. A prominent fact in therapeutic HBO is the acceleration of neoangiogenesis during granulation tissue formation. Angiogenesis is a highly orchestrated event, a diverse range of cells and angiogenesis factors are involved in the process. The formation of reactive oxidative species (ROS) during HBO has been controversially considered as signalling regulator for angiogenic factors, as well as harmful originator for oxidative stress-induced cyto- and geno-toxicity in cells. This thesis contributes to this interesting while challenging topic. The project starts with investigation the direct HBO effects on blood vessel in vitro under physiological conditions and pathological conditions. The data clearly show that a single HBO treatment does not induce oxidative stress and cell damage under physiological conditions. Nevertheless, under pathological conditions, HBO induces oxidative stress with more ROS formation and cell damage. Interestingly, no evidence has been shown that HBO alone or synergically promotes nitric oxide and vascular endothelial growth factor production in either condition. The response of blood vessel to HBO treatment is not explained by autocrine release of angiogenesis factors locally in the blood vessel. Next, HBO-induced intracellular calcium (Ca2) changes and DNA damage were investigated using cultured human umbilical vein endothelial cells. A single HBO treatment significantly elevates intracellular Ca2+ level without inducing cell damage. Furthermore, HBO treatment has small but significant effect on DNA migration when evaluated by comet assay (e. g. 6.8 ± 0.8 % comparing to 4.6 ± 0.2 % DNA in tail of air treatment). However, this effect is totally reversible after 24h recovery. Importantly, HBO treatment protects endothelial cells against subsequent oxidative stress attack, and an increased antioxidant capacity was found as reflected in higher ratio of GSH to GSSG. The findings suggest that the beneficial effect of HBO is possibly via HBO-induced adaptation in cellular redox status. However, the details of Ca2+ signalling and roles of antioxidants in HBO treatment are areas for further research. Keywords: Hyperbaric Oxygen, Oxidative Stress, Vascular Endothelial Growth Factor, Nitric Oxide, Endothelial Cells, Calcium, DNA Damage
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Perry, Leslie M. "Regulation of Alternative Sigma Factors During Oxidative and Ph Stresses in the Phototroph Rhodopseudomonas Palustris." Thesis, University of North Texas, 2014. https://digital.library.unt.edu/ark:/67531/metadc700009/.
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Rhodopseudomonas palustris is a metabolically versatile phototrophic α-proteobacterium. The organism experiences a wide range of stresses in its environment and during metabolism. The oxidative an pH stresses of four ECF (extracytoplasmic function) σ-factors are investigated. Three of these, σ0550, σ1813, and σ1819 show responses to light-generated singlet oxygen and respiration-generated superoxide reactive oxygen species (ROS). The EcfG homolog, σ4225, shows a high response to superoxide and acid stress. Two proteins, one containing the EcfG regulatory sequence, and an alternative exported catalase, KatE, are presented to be regulated by σ4225. Transcripts of both genes show similar responses to oxidative stress compared to σ4225, indicating it is the EcfG-like σ-factor homolog and controls the global stress response in R. palustris.
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Mullan, B. A. "Factors influencing endothelial function and arterial pulse wave morphology : the role of oxidative stress." Thesis, Queen's University Belfast, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398095.
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Sarrafee, Sara. "ROLE OF THE PORPHYROMONAS GINGIVALIS ECF SIGMA FACTOR, SIGH, IN OXIDATIVE STRESS RESPONSE." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1804.
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Periodontal disease affects a majority of the US population. Porphyromonas gingivalis is the major etiological agent for development and progression of the disease. P. gingivalis is a hemin-dependent, obligate anaerobe that is found predominantly in periodontal pockets in infected patients. So for, little is known regarding the mechanisms which allow P. gingivalis to survive and sustain itself in the oral cavity. To better understand the adaptive mechanisms of the bacterium to the varying conditions in the oral cavity, regulatory mechanisms must be characterized. Sigma factors (σ) are responsible for initiating transcription by guiding RNA polymerase binding to specific DNA promoter sites. There are several sigma factors present in P. gingivalis, yet their roles have to be identified. Previous unpublished data indicate that a gene coding for an extracytoplasmic function sigma factor (ECF), SigH, is differentially regulated by exposure to molecular oxygen. Different assays were conducted to assess any variation in survival and/or growth between wild-type and SigH deficient strains of P. gingivalis. The ability to grow and survive in the presence of oxidative stress was compared between the mutant deficient in SigH and that of the parental strain. In addition, transcriptional profiles of the two strains were compared. Our assays indicate that growth was slower in the presence of oxygen in the Sigh-deficient mutant with an average difference of 27% compared to the wild-type. Transcriptional profiling showed down-regulation of genes encoding key enzymes associated with oxidative stress protection and oxidative metabolism in the absence of SigH, indicating that the sigma factor is a positive regulator of transcription required for survival of the bacterium in the presence of oxygen. If oxygen sensitivity can be established for this ECF-σ factor, it will aid in better understanding of P. gingivalis’ ability to survive in the oral cavity despite the presence of oxygen.
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Helmersson, Johanna. "Prostaglandins and Isoprostanes in Relation to Risk Factors for Atherosclerosis : Role of Inflammation and Oxidative Stress." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4803.
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Takahashi, Ken-ichi. "Humoral factors for oxidative stress and regulation of body weight in patients with Obstructive Sleep Apnea." Kyoto University, 2008. http://hdl.handle.net/2433/124218.
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Nälsén, Cecilia. "Measurement and Evaluation of Antioxidant Status and Relation to Oxidative Stress in Humans." Doctoral thesis, Uppsala University, Clinical Nutrition Research, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6742.
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Numerous diseases are associated with reduced antioxidant defence and oxidative stress. The antioxidant defence includes dietary and endogenous antioxidants and involves complex interactions between them. The effects of dietary factors on antioxidant status and oxidative stress of healthy humans were investigated in the studies described in this thesis. Assays of plasma antioxidant capacity encompass interactions between various antioxidants. Although uric acid has an unclear function as an antioxidant, it is a major determinant of antioxidant capacity. We measured antioxidant capacity in the presence and absence of uric acid to provide more information on the application of measures of antioxidant capacity. Individuals with high dietary intakes of various antioxidants and antioxidant rich foods, especially when combined, had higher plasma antioxidant capacities than those with lower antioxidant intakes. However, there were no associations between dietary intake of antioxidants or antioxidant rich foods and the plasma concentration of F2-isoprostanes, which is considered a reliable biomarker for oxidative stress. Intakes of various doses of a mixture of bilberry juice and black tea, rich in flavonoids for four weeks, increased antioxidant capacity in some groups, but urine levels of F2-isoprostanes were not affected. There were substantial individual variations in responses to the drinks related to baseline antioxidant capacity. Supplementation with eicosapentaenoic acid and docosahexaenoic acid decreased the plasma levels of F2-isoprostanes, but not prostaglandin F2α formation or antioxidant capacity.
It was concluded that a high intake of foods rich in antioxidants is related to improved antioxidant status. After intake of foods rich in antioxidants, the antioxidant status may increase, but with considerable individual variation in the responses, which warrants further investigation. Lipid peroxidation in vivo is not easily affected by dietary antioxidants in healthy humans. Although n-3 fatty acids are highly unsaturated, they reduce nonenzymatic free radical-catalyzed lipid peroxidation, but not enzymatic lipid peroxidation.
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Leung, Man-hong, and 梁文康. "Investigating the role of the forkhead box transcription factor FOXM1 against oxidative stress and DNA damage in human embryonic stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/208595.
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Taqi, Aboubakr Mohamed Omar [Verfasser]. "Transcription factors mediated oxidative stress response in bovine follicular cells and preimplantation embryos / Mohamed Omar Taqi Aboubakr." Bonn : Universitäts- und Landesbibliothek Bonn, 2019. http://d-nb.info/1224966139/34.
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Singh, Sukhvinder Pal. "Postharvest oxidative stress in plums : mechanism and implications for storage and fruit quality." Thesis, Curtin University, 2010. http://hdl.handle.net/20.500.11937/551.
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Postharvest life and susceptibility to chilling injury (CI) in Japanese plums (Prunus salicina Lindl.) are greatly influenced by preharvest and postharvest factors. The phenomenon of postharvest oxidative stress has been implicated in affecting fruit quality, potential storability and susceptibility to development of physiological disorders during storage of fruits. Therefore, the investigations were carried out to understand the role of various factors, such as cultivar, harvest maturity, storage conditions (temperature and atmosphere composition), duration of storage and postharvest treatments, in the development of oxidative stress in Japanese plums, in relation to fruit quality and CI. The degree of lipid peroxidation and membrane integrity was measured by determining the activity of lipoxygenase enzyme, concentration of thiobarbituric acid–reactive substances, and amount of electrolyte leakage. The activities of antioxidant enzymes, superoxide dismutase, catalase, and peroxidase, were determined as a direct measure of the enzymatic antioxidant capacity. The activities of enzymes (ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione reductase, and glutathione–S–transferase) involved in the oxidation and regeneration of ascorbate (AA) and glutathione (GSH) were also determined to underpin the dynamics of the AA–GSH cycle. The concentrations of AA, dehydroascorbate (DHA), GSH, and oxidized glutathione (GSSG) were determined to compute the AA:DHA and GSH:GSSG ratios as the indicators of redox potential of fruit tissue. The total phenolics concentration and total antioxidant capacity were also determined as a part of the non–enzymatic antioxidants.The experimental data suggest that postharvest oxidative stress developed during fruit ripening in Japanese plums, but the rate was dependent on the climacteric behaviour of fruit. The climacteric cultivars, ‘Blackamber’ and ‘Amber Jewel’, showed a faster decline in the ability of antioxidative system to encounter the oxidative stress during fruit ripening as compared to ‘Angeleno’, a suppressed–climacteric cultivar. The delay in harvesting of ‘Amber Jewel’ plums by one week slightly improved fruit quality and the initial status of antioxidants than the commercial harvest. However, the fruit harvested at commercial maturity had better retention of antioxidative system during cold storage at 0°C for 3–4 weeks compared to the fruit from the delayed harvest. The changes in enzymatic and non–enzymatic antioxidants as a function of storage duration appear to be more prominent in providing protection against oxidative injury expressed as CI than their at–harvest status. The response of the antioxidative system in ‘Amber Jewel’ plums at 5°C was significantly better than at 0°C. But, the storage temperature of 5°C was not sufficiently low to inhibit the process of fruit ripening, resulting in limited storage life of 2 weeks. The multiple–point time course analysis of lipid peroxidation and changes in enzymatic and non–enzymatic antioxidants of ‘Blackamber’ plums revealed that the third week of storage is the critical point beyond which the capacity of antioxidative system to cope with the increasing oxidative stress from CI and fruit ripening began to decline, resulting in increased incidence and severity of CI during the extended periods of storage. Controlled atmospheres (CA) were found beneficial to reduce the levels of oxidative stress in ‘Blackamber’ plums.CA containing 1% O[subscript]2 + 3% CO[subscript]2 were effective in mitigating the oxidative stress during the 5 weeks of cold storage at 0–1°C, plus 6 days of shelf life at 21±1°C. The efficacy of CA (1% or 2.5% O[subscript]2 + 3% CO[subscript]2) in alleviating CI in ‘Blackamber’ plums could be further enhanced by the pre–storage treatment of fruit with 1–methylcyclopropene (1–MCP, 0.6 μL L[superscript]–[superscript]1). The combination of CA and 1–MCP exhibited synergistic effects on the alleviation of oxidative stress, resulting in enhanced storage life up to 8 weeks, plus 6 days of shelf–life. The role of nitric oxide (NO) as an antioxidant was also investigated in order to retard fruit ripening, delay the onset of senescence and development of oxidative stress in the Japanese plums. Postharvest NO fumigation (10 or 20 μL L[superscript]–[superscript]1) delayed the fruit ripening and maintained quality for 9–12 days in ‘Amber Jewel’ and ‘Blackamber’ plums at 21±1°C. NO fumigation was also beneficial to reduce the symptoms of CI during cold storage of ‘Amber Jewel’ and ‘Blackamber’ plums for 5–6 weeks at 0°C, plus 5 days of shelf–life at 21±1°C. The positive effects of NO fumigation on the enzymatic and non–enzymatic antioxidants in addition to reduced rates of lipid peroxidation were associated with the enhanced chilling tolerance in Japanese plums. The response of ‘Amber Jewel’ to postharvest NO fumigation was significantly better than ‘Blackamber’.In conclusion, the development of oxidative stress in Japanese plums was influenced by cultivar, harvest maturity, cold storage (temperature, duration and atmosphere composition), and postharvest treatments with NO and 1–MCP. The mitigation of oxidative stress by manipulation of postharvest storage conditions and treatments can be achieved to maintain fruit quality and reduce the incidence and severity of CI in Japanese plums.
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Castillo, Andreo Esther. "Regulación por estrés oxidativo de la actividad del factor de transcripción Pap1 de Schizosaccharomyces pombe." Doctoral thesis, Universitat Pompeu Fabra, 2005. http://hdl.handle.net/10803/7089.
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Las especies reactivas del oxígeno (ROS), superóxido (O2o-), peróxido de hidrógeno (H2O2), y radical hidroxilo (OHo), se generan a partir de la reducción parcial del oxígeno molecular durante procesos metabólicos como la respiración o tras la exposición a ciertos agentes ambientales como las radiaciones UV. Estas ROS pueden reaccionar con biomoléculas como lípidos, proteínas y DNA e inactivar su función, por lo que las células han desarrollado actividades enzimáticas que se encargan de mantener niveles no-tóxicos de estos oxidantes. Se llama estrés oxidativo a la situación en la cual se produce un incremento en la concentración intracelular de ROS como consecuencia de un aumento en la generación o una disminución en la degradación de las mismas. En respuesta a estrés oxidativo, la célula activa rutas de señalización y factores de transcripción específicos que activan la expresión de proteínas antioxidantes encargadas de reestablecer los niveles redox intracelulares y de reparar los desperfectos causados por estos oxidantes. La levadura Schizosaccharomyces pombe es un organismo modelo ideal para el estudio de las respuestas a estrés oxidativo en las células eucariotas ya que posee sensores específicos a estrés oxidativo como el factor de transcripción Pap1 (pombe AP-1-like) y rutas de respuesta global a estrés, como las descritas en las células de mamífero, que son activadas por diferentes tipos de estrés. En el centro de esta ruta de respuesta global a estrés se encuentra la MAPK (Mitogen-activated protein kinase) Sty1.
El factor de transcripción Pap1, de localización citoplasmática basal, se acumula en el núcleo en respuesta a estrés oxidativo. Este cambio de localización subcelular es debido a la inhibición del exporte nuclear dependiente de Crm1, aunque se desconocía el mecanismo molecular utilizado por este factor de transcripción para sensar y responder a oxidantes como H2O2 y dietilmaleto (DEM). Los resultados obtenidos indican que H2O2 oxida de forma reversible dos residuos de cisteína de Pap1 induciendo, seguramente, la formación de un puente disulfuro intramolecular, mientras que, DEM actúa como un agente alquilante que modifica de forma irreversible los residuos de cisteína del dominio C-terminal de Pap1.
El gen que codifica para el factor de transcripción Pap1 fue aislado inicialmente como un gen que, en elevado número de copias, confería a las células un fenotipo de resistencia a ciertas drogas como estaurosporina. Esto es debido a que, tras acumularse en el núcleo en respuesta a estrés oxidativo, Pap1 activa la transcripción de genes implicados tanto en la respuesta antioxidante como en la resistencia a multidrogas. Todos aquellos genes que, al igual que pap1 fueron identificados por su implicación en la resistencia a multidrogas, codifican para proteínas que regulan la actividad del factor de transcripción Pap1. hba1 fue el único gen relacionado con resistencia a multidrogas, cuyo producto génico, una proteína con un dominio de unión a Ran (Ran-binding domain), Hba1, no había sido relacionado con la actividad de Pap1. Uno de los objetivos de mi trabajo experimental era el de determinar si Hba1 tenía un papel en la regulación de la actividad de Pap1.
Nuestros resultados indican que la proteína Hba1, localizada en el nucleoplasma de la célula, participa en el exporte nuclear mediado por Crm1 de ciertas proteínas como el factor de transcripción Pap1 y la MAPK Sty1, aunque no de otras como la proteína PKI. Por ello, la pérdida de función de Hba1, por sobreexpresión o deleción del gen hba1, induce la localización nuclear constitutiva de Pap1 y Sty1 en ausencia de estrés. Esta localización nuclear de Pap1 es suficiente para la activación transcripcional de sus genes diana. Por lo tanto, el fenotipo de resistencia aumentada a multidrogas de las cepas en las que se ha perdido la actividad de la proteína Hba1, es debido a la acumulación de Pap1 en el núcleo en condiciones de no-estrés.
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Medlow, Paul Wallace. "The effects of aerobic exercise on oxidative stress and cardiovascular risk factors in aging and type II diabetes mellitus." Thesis, University of Ulster, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.601214.
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The oxidation of low-density lipoproteins (LDL) is considered a key step in the development and progression of atherosclerosis. Single bouts of aerobic exercise cause transient increases in free radical production that may enhance the susceptibility of LDL to oxidation and create a more atherogenic LDL particle. In contrast, chronic exercise has often been considered an effective tool in improving metabolic profile through changes in aerobic capacity, lipid profile, fuel utilization and oxidative stress in both healthy and disease populations. Despite this, less is known about how it may benefit the prevention of LDL oxidation and the mechanisms by which this may occur, particularly in aged and patients with type II diabetes who have oxidative stress. The primary aim of the work contained in this thesis, is to examine the effects of aerobic exercise on the susceptibility of LDL to oxidation in both young, aged and type II diabetic subjects. The findings of study 1 demonstrate that an acute bout of moderate intensity exercise can increase the susceptibility of LDL III in both young and aged subjects regardless of any change in LDL lipid composition. Study 2 demonstrates that chronic aerobic exercise of moderate intensity is effective at improving the resistance of the LDL I sub fraction against oxidation, as shown by an increase in T1I2max, despite no change in LDL lipid composition. This intervention was also beneficial in altering maximal aerobic capacity in both young and aged subjects. Study 3 demonstrates that chronic low and moderate intensity aerobic exercise has no effect on LDL oxidative susceptibility. However, chronic moderate intensity exercise increased catalase activity and decreased protein oxidation. The collective findings of this work provide evidence that acute exercise may increase LDL oxidation while chronic exercise may prevent the oxidation of LDL particularly in aged subjects. Further research with greater subject numbers is required to determine the precise mechanism by which exercise influences the susceptibility of LDL oxidation.
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Mistry, Hiten. "Selenium, selenoproteins and factors which might interact with them relating to oxidative stress, in normal and pre-eclamptic pregnancies." Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491024.
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Pre-eclampsia (PE) is a pregnancy specific condition that affects 2-3% of women. At present the cause of PE is unknown, however the main pathological features are impaired placentation, with inadequate invasion of the spiral arteries by syncytiotrophoblasts, and systemic endothelial damage, contributing to increased perinatal and maternal morbidity and mortality. PE may have life time consequences for the fetus in terms of greater predisposition to adult cardiovascular disease.
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Singh, Indu, and indu singh@rmit edu au. "The influence of antioxidants on thrombotic risk factors in healthy population." RMIT University. Medical Sciences, 2008. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20081205.121719.
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Oxidative damage has been suggested to play a key role in the pathogenesis of atherosclerosis and other cardiovascular disease. Increased free radical production induced by oxidative stress can oxidise low density lipoproteins, activates platelets, induces endothelial dysfunction and disturbs glucose transport by consuming endogenous antioxidants. Using a combination, of in vitro and in vivo experimental models, the primary aims of the studies undertaken for this thesis were to examine whether different antioxidants could negate risk factors leading to thrombosis, atherosclerosis and other cardiovascular diseases. The studies utilised the mechanisms involved in platelet activity and glucose uptake by skeletal muscle myotubes. The first study determined if olive leaf extract would attenuate platelet activity in healthy human subjects. Blood samples (n=11) were treated with five different concentrations of extract of Olea europaea L. leaves ranging from 5.4£gg/mL to 54£gg/mL. A significant reduction in platelet activity (pless than0.001) and ATP release from platelets (p=0.02) was observed with 54£gg/mL olive leaf extract. The next crossover study compared the effect of exercise and antioxidant supplementation on platelet function between trained and sedentary individuals. An acute bout of 1 hour exercise (sub maximal cycling at 70% of VO2max) was used to induce oxidative stress in 8 trained and 8 sedentary male subjects, before and after one week supplementation with 236 mg/day of cocoa polyphenols. Baseline platelet count and ATP release increased significantly (pless than0.05) after exercise in all subjects. Baseline platelet numbers in the trained were higher than in the sedentary (235¡Ó37 vs. 208¡Ó34 x109/L, p less than 0.05), whereas platelet activation in trained subjects was lower than sedentary individuals (51¡Ó6 vs. 59¡Ó5%, p less than0.05). Seven days of cocoa polyphenol supplementation did not change platelet activity compared to the placebo group. The third study determined the effect of 5 weeks of either 100mg/day £^-Tocopherol (n=14), 200mg/d £^-Tocopherol (n=13) or placebo (n=12) on platelet function, lipid profile and the inflammatory marker C-reactive protein. Blood £^-tocopherol concentrations increased significantly (pless than0.05) relative to dose. Both doses attenuated platelet activation (pless than0.05). LDL cholesterol, platelet aggregation and mean platelet volume were decreased by 100mg/d £^-tocopherol (all pless than0.05). The final study determined the effect of glucose oxidase induced oxidative stress and £^-tocopherol treatment on glucose transport and insulin signalling in cultured rat L6 muscle cells. One hour treatment with 100mU/mL glucose oxidase significantly decreased glucose uptake both with and without 100nM insulin stimulation (pless than0.05). Pre-treatment with 100ÝM and 200ÝM £^-tocopherol partially protected cells from the effect of glucose oxidase, whereas 200ÝM £^-tocopherol restored both basal and insulin stimulated glucose transport to control levels. Glucose oxidase-induced oxidative stress did not impair basal or insulin stimulated phosphorylation of Akt or AS160, but 200ÝM £^-tocopherol improved insulin-stimulated phosphorylation of these proteins. In summary, the results from the studies undertaken for this thesis provide evidence that antioxidant supplementation maintains normal platelet function, exerts a positive effect on blood lipid profile and improves glucose uptake in normal healthy asymptomatic population as well as under conditions of induced oxidative stress. Antioxidants including foods rich in cocoa, olive and gamma tocopherol have the potential to combat oxidative stress induced risk factors leading to cardiovascular diseases.
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Wang, Zhenchao. "Role of Oxidative Stress, Growth Factors and Apoptosis in Diabetic Nephropathy and Regulation of Preoptic Area Regulatory Factor-2 Expression by Insulin/IGF-1." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1305040037.
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Alkazemi, Dalal Usamah Zaid. "Modulating factors of serum oxysterol concentrations in daughters from gestational diabetes and non-gestational diabetes." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100757.
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Pregestational and gestational diabetes (GDM) places the mother and her offspring at an increased risk for later development of insulin resistance and type 2 diabetes. Oxidative stress may mediate long-term disturbances in glucose homeostasis associated with type 2 diabetes and the metabolic syndrome. This thesis describes a cross-sectional study examining serum concentrations of free radical generated oxysterols as markers of oxidative stress in a cohort of teenage daughters from pregnancies with and without GDM. Daughters of GDM-pregnancies had a tendency of higher levels of serum oxysterols (7beta-hydroxycholesterol); however, this difference was not statistically significant after adjustment for total cholesterol. Serum oxysterols were significantly correlated with obesity measures such as waist circumference and BMI, which likely accounted for the tendency for higher measures of oxysterol concentrations in the GDM daughters. Oxysterols represent potentially important biomarkers for oxidative stress in adolescent girls as their levels track with the metabolic syndrome risk factors.Le diabète pré-gestationnel et le diabète de gestation (DG) augmentent le risque dedéveloppement d'une future résistance à l'insuline et de diabète de type 2 autant pourla mère que pour l'enfant. Le stress oxydatif est un facteur potentiel impliqué dans ledéséquilibre du glucose sanguin associé au diabète de type 2 et au syndromemétabolique. La présente thèse est une étude sectionnelle croisée, ayant pour but demesurer des marqueurs du stress oxidatif, notamment la concentration des oxystérolsgénérés par les radicaux libres dans le sérum d'adolescentes, nées de mères ayantprésenté ou non un diabète de gestation. Nos résultats montrent des concentrationsd'oxystérols (7P-hydroxycholesterol) plus élevées dans le sérum de filles issues degestations diabétiques à comparer aux filles de mères n'ayant pas eu de DG.Cependant, la différence entre les deux groupes n'était pas statistiquementsignificative après un ajustement au cholestérol total. La concentration d'oxystérolsétait significativement corrélée aux marqueurs d'obésité, notamment la circonférencede la taille et l'index de masse corporelle, possiblement à l'origine de la tendance desoxystérols à être plus élevés dans le cas des adolescentes issues de gestationsdiabétiques.
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Rytter, Elisabet. "Effect of Dietary Antioxidants on Oxidative Stress, Inflammation and Metabolic Factors : Studies in Subjects with Overweight and with Type 2 Diabetes." Doctoral thesis, Uppsala universitet, Oxidativ stress och inflammation, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-134938.
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Observational studies have indicated that fruit and vegetables, and dietary antioxidants may play an important role in reducing the risk of chronic diseases, potentially by affecting pathogenic mechanisms such as oxidative stress and inflammation. Clinical trials investigating the effects of supplementation with single or a few antioxidants in high doses have, however, shown inconsistent results and thus have not been able to support the observational findings. It was therefore hypothesised that a supplement, containing a combination of antioxidants mainly extracted from fruit and vegetables, and supplied at moderate doses, might act more beneficially than single antioxidants given at pharmacological doses. The effects of such a supplement were investigated in two interventional studies described in this thesis. The effects on antioxidant status, metabolic control, oxidative stress and inflammation were investigated in overweight men and in patients with type 2 diabetes, subjects that could be expected to have elevated levels of oxidative stress and inflammatory activity. The results of the studies did not support the hypothesis that supplementation with antioxidants from fruit and vegetables may have beneficial effects by counteracting oxidative stress and inflammation, despite markedly increased plasma antioxidant concentrations. However, interesting associations were observed in diabetes patients at baseline between intake of antioxidant rich food as well as levels of antioxidants in plasma, and markers of oxidative stress and inflammation. These associations are compatible with the hypothesis that a high intake of fruit and vegetables and dietary antioxidants decrease oxidative stress levels, have anti-inflammatory effects and a beneficial influence on glycaemic control. The results also indicated that glycaemic control may affect the level of oxidative stress. The absence of beneficial effects from antioxidants might to some extent be explained by the initial levels of oxidative stress and inflammation and by the antioxidative status in the subjects included in the studies. Since the levels generally were comparable with those observed in healthy subjects, this might have decreased the ability to observe any beneficial effects of supplementation with additional antioxidants. Continued investigations are needed to characterise the individuals who potentially might benefit from antioxidant supplementation. In view of apparent positive effects from a high intake of fruit and vegetables found in observational studies and until more knowledge is available from interventional trials about possible benefits and potential risks of antioxidant supplementation it still seems reasonable to recommend a diet rich in fruit and vegetables.
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Yu, Xin. "STUDIES OF FACTORS AFFECTING INTRACELLULAR TOXICITY OF THE SCA7 DISEASE PROTEIN ATAXIN - 7 : FOCUS ON ATAXIN-7 DEGRADATION AND OXIDATIVE STRESS." Licentiate thesis, Stockholms universitet, Institutionen för neurokemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-64167.
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Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expansion of CAG/polyglutamine repeats. Proteins carrying expanded polyglutamine (polyQ) domains are suggested to be resistant to degradation and aggregate. Furthermore, a negative correlation between aggregation and toxicity has been shown. So far, little is known about the turn-over rate and degradation of the SCA7 disease protein ataxin-7 (ATXN7) and how this protein induces cellular toxicity. For the studies in this thesis work, we constructed stable inducible PC12 cell lines expressing GFP-tagged ATXN7 with 10 or 65 glutamines (Qs). Using these cell lines, we studied the turn-over of ATXN7 and the relationship between mutant ATXN7 and oxidative stress. We showed that ATXN7 with a normal glutamine repeat (ATXN7Q10-GFP) has a short half-life and is mainly degraded by the UPS. In cells expressing expanded ATXN7 (ATXN7Q65-GFP), aggregation and reduced viability was observed. The aggregation increased the half-life of mutant ATXN7. For expanded full-length ATXN7, UPS was still the main degradation pathway; however autophagy also played a role in clearance of soluble ATXN7 fragments and possibly in aggregated ATXN7 material. Moreover, activation of autophagy reduced the level of aggregation and ameliorated the toxicity in cells expressing mutant ATXN7. From this study, we could get the conclusion that although expansion of the polyQ repeat increases the stability of expanded ATXN7, the protein can still be degraded via both UPS and autophagy. Furthermore, stimulation of autophagy could ameliorate the expanded ATXN7 toxicity and could therefore be a potential therapeutic approach for SCA7. Regarding the role of oxidative stress we showed that expression of mutant ATXN7 leads to increased ROS levels and oxidative stress. Treatment with an antioxidant or blockage of NADPH oxidase complexes (NOX) decreased ATXN7 aggregation, the levels of ROS and ameliorated ATXN7 induced toxicity. Based on these results, we suggest that mutant ATXN7 cause increased ROS production from NOX and antioxidants treatment and or inhibition of NADPH-oxidase might potentially be used as a therapeutic strategy in SCA7.At the time of defence the following paper was unpublished and had a status as follows: Paper 2: Manuscript
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Svensson, Michael B. "Endogenous antioxidants in human skeletal muscle and adaptation in energy metabolism : with reference to exercise-training, exercise-related factors and nutrition /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-433-X.
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Chan, Kevin Ki Fai. "Factors influencing arbovirus transmission: vector competence and the effects of virus infection on repellent response, oxidative stress, and glutathione-S-transferase activity." Diss., Virginia Tech, 2020. http://hdl.handle.net/10919/104393.
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Zika (ZIKV), La Crosse (LACV), and Cache Valley (CVV) viruses are mosquito-vectored diseases that cause significant morbidity and mortality in humans and animals. Transmission of these viruses are dependent on numerous factors including vector competence and the effects of mosquito-virus interactions. We conducted vector competence studies of local Aedes and Culex mosquitoes for ZIKV and CVV, and found that all Aedes mosquitoes were competent for CVV and only Aedes albopictus and Aedes japonicus were competent for ZIKV. Vector competence for CVV was dose-dependent, where mosquitoes orally infected with high titers developed higher transmission rates. We also found that vector competence for ZIKV was limited by midgut and salivary gland barriers. Second, we looked at the effects of LACV and ZIKV infection on repellent response in Aedes mosquitoes and found that infected mosquitoes were refractory to low concentrations of DEET, picaridin, and PMD. Increasing concentrations of the repellents to ≥10% was able to increase percent protection (%p) against infected and uninfected mosquitoes. Lastly, we determined the effects of ZIKV and LACV infection on oxidative stress and glutathione-S-transferase (GST) activity in Aedes albopictus. Virus infection had no effect on oxidative stress, but GST activity was significantly different for mosquitoes 3-days post-exposure. We found that oxidative stress levels and GST activity had an inverse relationship for infected and uninfected mosquitoes, where oxidative stress decreased and GST activity increased over the 10-day test period. This indicates that GSTs may aid in controlling byproducts of oxidative stress. The results from this entire study identified competent vectors for emerging arboviruses and demonstrated the behavioral and physiological effects of virus infection in the mosquito vector.Doctor of Philosophy
Zika (ZIKV), La Crosse (LACV), and Cache Valley (CVV) viruses are transmitted by mosquitoes and can make humans and animals very sick. There are many biological factors that determine if a mosquito can transmit a virus and these viruses can change the biology of a mosquito. We conducted laboratory studies to see if Aedes and Culex mosquitoes can transmit ZIKV and CVV. We found that all Aedes mosquitoes were able to transmit CVV and only the Asian tiger mosquito and Asian rock pool mosquito were able to transmit ZIKV. Mosquitoes infected with high amounts of CVV developed higher transmission rates. We also found that transmission of ZIKV was limited by barriers in the mosquito midgut and salivary glands. Second, we looked at the effects of LACV and ZIKV infection on how Aedes mosquitoes respond to repellents and found that infected mosquitoes were less sensitive to low concentrations of DEET, picaridin, and PMD. Increasing concentrations of the repellents to 10% or higher was able to provide adequate protection against infected and uninfected mosquitoes. Lastly, we determined the effects of ZIKV and LACV infection on oxidative stress and glutathione-S-transferase (GST) activity in the Asian tiger mosquito. Virus infection did not change oxidative stress, but GST activity was higher in infected mosquitoes tested after 3 days after infection. We found that oxidative stress decreased and GST activity increased over the 10-day test period. This indicates that GSTs may help control damaging products from oxidative stress. The results from this entire study identified what mosquitoes were able to transmit emerging mosquito-borne viruses and demonstrated the biological effects of virus infection in the mosquitoes.
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Gumpper, Kristyn Nicole. "Maintaining Cardiac and Gastric Physiology: TRIM Proteins as Central Factors in Regulation of Organ Homeostasis at the Cellular Level." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563287863754715.
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Lee, Bo Young. "Signaling events in activity dependent neuroprotection, neurodegeneration, and synaptic plasticity." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1180458484.
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Miralles, Pérez Bernat. "Effects of Fish Oil and its Combination with Grape Seed Polyphenols or Buckwheat D-Fagomine on Cardiometabolic Risk Factors and Oxidative Stress in Rats." Doctoral thesis, Universitat Rovira i Virgili, 2021. http://hdl.handle.net/10803/672213.
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En les darreres dècades, les prevalences d’obesitat, de dislipèmia aterogènica i de síndrome metabòlica han augmentat considerablement a nivell mundial. La resistència a la insulina és una característica comuna en aquests trastorns cardiometabòlics. La patogènesi de la resistència a la insulina està clarament relacionada amb l’estrès oxidatiu, la inflamació i l’acumulació de lípids bioactius com els diacilglicerols i les ceramides. Els àcids grassos poliinsaturats ω-3 (AGPI ω-3) presents en l’oli de peix, l’àcid eicosapentaenoic (EPA) i l’àcid docosahexaenoic (DHA), s’associen a un menor risc de desenvolupar trastorns cardiometabòlics. No obstant això, quan es proporciona en excés, el DHA pot provocar efectes perjudicials sobre la salut. La combinació de compostos bioactius pot ser una estratègia preventiva per protegir contra l’aparició de trastorns cardiometabòlics. L’objectiu d’aquest treball és avaluar l’efecte de l’oli de peix i la seva combinació amb els polifenols de llavors de raïm o la D-fagomina del blat sarraí sobre els factors de risc cardiometabòlics i l’estrès oxidatiu en rates sanes i en rates alimentades amb una dieta rica en greixos. La suplementació amb l’oli de peix ric en DHA millora diversos factors de risc cardiometabòlics, però augmenta el dany oxidatiu a biomolècules en rates sanes. La suplementació combinada amb l’oli de peix amb una proporció de EPA/DHA 1:1 i els polifenols de llavors de raïm tendeix a atenuar l’estrès oxidatiu, i afecta significativament el contingut de lípids bioactius al fetge de rates alimentades amb una dieta rica en greixos. La suplementació combinada amb l’oli de peix amb una proporció de EPA/DHA 1:1 i la D-fagomina de blat sarraí exerceix efectes beneficiosos sobre l’estrès oxidatiu i sobre alguns factors de risc cardiometabòlics en rates alimentades amb una dieta rica en greixos. Augmentar la ingesta dietètica d’AGPI ω-3 mitjançant suplements d’oli de peix amb una proporció de EPA/DHA 1:1, de forma individual o combinada amb els polifenols o la D-fagomina, pot ser una estratègia nutricional útil per protegir contra els mecanismes implicats en l’aparició de trastorns cardiometabòlics en individus sans i en individus amb un alt risc de malaltia.En las últimas décadas, las prevalencias de obesidad, de dislipidemia aterogénica y de síndrome metabólico han aumentado a nivel mundial. La resistencia a la insulina es una característica común en estos trastornos cardiometabólicos. La patogenia de la resistencia a la insulina está claramente relacionada con el estrés oxidativo, la inflamación y la acumulación de lípidos bioactivos como los diacilgliceroles y las ceramidas. Los ácidos grasos poliinsaturados ω-3 (AGPI ω-3) presentes en el aceite de pescado, el ácido eicosapentaenoico (EPA) y el ácido docosahexaenoico (DHA), están asociados a un menor riesgo de desarrollar trastornos cardiometabólicos. Sin embargo, cuando se administra en dosis excesivas, el DHA puede provocar efectos perjudiciales para la salud. La combinación de compuestos bioactivos puede ser una estrategia preventiva para proteger contra la aparición de trastornos cardiometabólicos. El objetivo de este trabajo es evaluar los efectos del aceite de pescado y su combinación con polifenoles de semillas de uva o D-fagomina del trigo sarraceno sobre los factores de riesgo cardiometabólico y el estrés oxidativo en ratas sanas y en ratas alimentadas con una dieta rica en grasas. La suplementación con el aceite de pescado rico en DHA mejora varios factores de riesgo cardiometabólico, pero aumenta el daño oxidativo de las biomoléculas en ratas sanas. La suplementación combinada con el aceite de pescado con una proporción EPA/DHA 1:1 y los polifenoles de semillas de uva tiende a reducir el estrés oxidativo y modula significativamente el contenido de lípidos bioactivos en el hígado de ratas alimentadas con una dieta alta en grasas. La suplementación combinada con el aceite de pescado con una proporción EPA/DHA 1:1 y la D-fagomina del trigo sarraceno tiene efectos beneficiosos sobre el estrés oxidativo y sobre algunos factores de riesgo cardiometabólico en ratas alimentadas con una dieta rica en grasas. Aumentar la ingesta dietética de AGPI ω-3 mediante suplementos de aceite de pescado con una proporción EPA/DHA 1:1, de forma individual o combinada con los polifenoles o la D-fagomina, puede ser una estrategia nutricional útil para proteger contra los mecanismos implicados en el desarrollo de trastornos cardiometabólicos en individuos sanos y en individuos con un alto riesgo de enfermedad.
The past few decades have seen an alarming increase in the worldwide prevalence of obesity, atherogenic dyslipidemia, and metabolic syndrome. Insulin resistance is a common characteristic in these cardiometabolic disorders. The pathogenesis of insulin resistance is clearly related to oxidative stress, inflammation as well as accumulation of bioactive lipids such as diacylglycerols and ceramides. The ω-3 polyunsaturated fatty acids (ω-3 PUFA) from fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with lower risk for developing cardiometabolic disorders. Nevertheless, when provided in excess, DHA may lead to deleterious effects on health. Combining bioactive compounds may be a powerful preventive strategy to protect against the onset of cardiometabolic disorders. The aim of the present work is to explore the influence of fish oil and its combination with grape seed polyphenols or buckwheat D-fagomine on cardiometabolic risk factors and oxidative stress in healthy rats and in rats fed a high fat diet. The supplementation with the fish oil rich in DHA beneficially affects several cardiometabolic risk factors, but increases oxidative damage to biomolecules in healthy rats. The combined supplementation with fish oil containing EPA/DHA 1:1 and grape seed polyphenols tends to attenuate oxidative stress, and significantly modulates abundances of bioactive lipids in the liver of rats fed a high fat diet. The combined supplementation with fish oil containing EPA/DHA 1:1 and buckwheat D-fagomine exerts beneficial influence on oxidative stress and on some related cardiometabolic risk factors in rats fed a high fat diet. The increase in dietary intake of ω-3 PUFA from fish oil supplements containing EPA/DHA 1:1, alone or combined with polyphenols or D-fagomine, may be a useful nutritional strategy to protect against the mechanisms underlying the onset of cardiometabolic disorders in healthy individuals and in individuals at high risk of disease.
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Chung, Wai Shing. "Investigation on the correlation between redox changes and oxidative stress in diabetes, and their role in transcription factors activation in vitro and in vivo." HKBU Institutional Repository, 2002. http://repository.hkbu.edu.hk/etd_ra/428.
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Rowe, Derrick. "Secreted Factors from Human Umbilical Cord Blood Cells Protect Oligodendrocytes from Ischemic Insult." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3323.
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Oligodendrocytes (OL)s are the dominant cell type in the white matter and are integral for synaptic transmission essential for proper neuronal communication between brain areas. Previous studies have shown that intravenous administration of the mononuclear fraction of human umbilical cord blood (HUCB) cells in rat models of stroke reduced white matter injury, gray matter injury and behavioral deficits. Yet the mechanisms used by HUCB cells remain unknown in ischemic injury. These studies will investigate both in vitro and in vivo approaches to elucidate this mechanism in OLs. When mature primary OLs were coincubated with HUCB cells, HUCB cells secreted soluble factors that reduced cell death in OLs exposed to OGD. Microarray analysis revealed that HUCB cell treatment induced OL gene changes. These changes included genes involved in cell proliferation, signaling, anti-oxidant activity, and myelination. To extend these findings, the middle cerebral artery occlusion (MCAO) model was used to assess the expression profile of protein products of gene changes observed in vitro. The in vivo data mirrored in vitro data in that metallothionein 3 (Mt3), peroxiredoxin 4 (Prdx4), myelin oligodendrocyte glycoprotein (Mog), U2AF homology kinase 1(Uhmk1), and insulin induce gene 1(Insig1) were upregulated in OLs of the white matter tract adjacent to the infarct. Furthermore, double immunofluorescence staining determined that OLs expressed these proteins. Other reports have shown that HUCB cells secrete soluble factors related to cellular protection, including interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10). Other factors are known for their proliferative actions, such as vascular endothelial growth factor (VEGF), BDNF, platelet derived growth factor B (PDGF-B), leukemia inhibitory factor (LIF), and granulocyte colony stimulating factor (GCSF) all of which converge on the Akt survival pathway. Given these findings we hypothesize that Akt activation is integral to HUCB cell mediated OL protection. In models of excitotoxicity, the addition of Akt inhibitor IV blocked HUCB cell mediated protection in OL cultures exposed to 24 hrs OGD. In vivo, HUCB cell treatment increased Akt activation, antioxidant protein expression and decreased caspase 3 cleavage in the external capsule in a time dependent manner. The next series of experiments determine whether the soluble factors secreted by HUCB cells could replace HUCB cells as treatment. LIF expression is increased in HUCB cells as compared to peripheral blood and as previously mentioned, LIF is secreted by HUCB cells. Additionally, LIF rescued OLs from spinal cord and experimental autoimmune encephalomyelitis injury. Thus LIF was investigated. LIF protected OL subjected to 24 hr OGD, increased antioxidant Prdx4 gene expression and reduced reactive oxygen species production. Additionally the inclusion of Akt inhibitor IV blocked LIF induced OL protection. Similar results were obtained when GCSF was evaluated. All these findings indicate that HUCB cell mediated OL/white matter protection is due to the soluble factors secreted by the mononuclear population of these cells. These soluble factors including LIF activate cellular machinery leading to enhanced cellular survival. Here we found a specific survival pathway activated by soluble factors released from HUCB cells, leading to Akt activation. Akt activation arrests stroke induced apoptosis and reduced the expansion of the infarct, promoting functional recovery from acute ischemic injury.
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Fitsanakis, Vanessa A., Kimberly N. Thompson, Sarah E. Deery, Dejan Milatovic, Zak K. Shihabi, Keith M. Erikson, Russell W. Brown, and Michael Aschner. "A Chronic Iron-Deficient/High-Manganese Diet in Rodents Results in Increased Brain Oxidative Stress and Behavioral Deficits in the Morris Water Maze." Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/6346.
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Iron deficiency (ID) is especially common in pregnant women and may even persist following childbirth. This is of concern in light of reports demonstrating that ID may be sufficient to produce homeostatic dysregulation of other metals, including manganese (Mn). These results are particularly important considering the potential introduction of the Mn-containing gas additive, methyl cyclopentadienyl manganese tricarbonyl (MMT), in various countries around the world. In order to model this potentially vulnerable population, we fed female rats fed either control (35 mg Fe/kg chow; 10 mg Mn/kg chow) or low iron/high-manganese (IDMn; 3.5 mg Fe/kg chow; 100 mg Mn/kg chow) diet, and examined whether these changes had any long-term behavioral effects on the animals' spatial abilities, as tested by the Morris water maze (MWM). We also analyzed behavioral performance on auditory sensorimotor gating utilizing prepulse inhibition (PPI), which may be related to overall cognitive performance. Furthermore, brain and blood metal levels were assessed, as well as regional brain isoprostane production. We found that treated animals were slightly ID, with statistically significant increases in both iron (Fe) and Mn in the hippocampus, but statistically significantly less Fe in the cerebellum. Additionally, isoprostane levels, markers of oxidative stress, were increased in the brain stem of IDMn animals. Although treated animals were indistinguishable from controls in the PPI experiments, they performed less well than controls in the MWM. Taken together, our data suggest that vulnerable ID populations exposed to high levels of Mn may indeed be at risk of potentially dangerous alterations in brain metal levels which could also lead to behavioral deficits.
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Kegler, Aline. "NEUROINFLAMAÇÃO E VIA APOPTÓTICA NA EPILEPSIA." Universidade Federal de Santa Maria, 2015. http://repositorio.ufsm.br/handle/1/11251.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorEpilepsy is a neurological disease that affects around 1% of world population, with neurobiological, neurochemical, cognitive and psychological consequences. Despite the good prognosis, the high number of epilepsy patients who have refractory seizures to medicine, reflects lack of a better understanding about excitotoxic disorders characteristic of the disease. So, the aim of the study was to investigate if there is an association between apoptotic markers and inflammation pathway in epileptic subjects and those without the disease. Blood samples were collected from subjects with epilepsy and were measured protein carbonyl, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-لا), acetylcholinesterase (AChE), caspases (CASP8 and CASP3) and picogreen (PG). The results showed an increase in all analyzed biochemistry parameters from epilepsy subjects when compared to healthy, suggesting that there is a relation between this disease with apoptotic and inflammatory markers. Furthermore, there was a positive correlation between TNF-α with CASP 8 and 3. IFN-لا was just correlated with caspase 3. The correlation between analyzed parameters with seizure severity and antiepileptic drugs (AEDs) treatment was not significant, indicating that medicine administration and symptoms improve did not influence obtained results. So, our results suggest that epileptic seizures can induce the creation of a vicious circle between neuroinflammation and cell death, resulting in DNA damage in epilepsy patients. Furthermore, we suggest that AEDs acting in TNF-α or IFN-لا pathway could represent an adjunctive therapy in epilepsy patients treatment.
A epilepsia é uma doença neurológica que afeta em torno de 1% da população mundial, tendo consequências no âmbito neurobiológico, neuroquímico, cognitivo e psicológico. Apesar do bom prognóstico, o elevado número de pacientes com epilepsia, que apresentam convulsões refratárias aos medicamentos, reflete a falta de um melhor entendimento dos distúrbios excitotóxicos característicos desta doença. A partir disto, o objetivo deste estudo foi investigar se existe uma associação entre os marcadores apoptóticos e a via inflamatória em indivíduos epilépticos e naqueles sem a doença. Amostras de sangue foram coletadas de pacientes com epilepsia e posteriormente foram analisados os níveis de proteína carbonil, fator de necrose tumoral alfa (TNF-α), interferon gama (INF-لا), acetilcolinesterase (AChE), caspases (CASP8 e CASP3) e picogreen (PG). Os resultados mostraram um aumento em todos os parâmetros bioquímicos analisados no sangue de pacientes com epilepsia quando comparado aos controles. Além disso, foi observada uma correlação positiva entre TNF-α com as caspases (8 e 3). O IFN-لا correlacionou-se apenas com os níveis da caspase 3. A correlação entre os parâmetros analisados com a gravidade das crises epilépticas e o tratamento com fármacos antiepilépticos (FAEs) não foi significativa, indicando que a administração de medicamentos para controle das crises e melhora dos sintomas não influenciou nos resultados obtidos. Dessa forma, os nossos dados sugerem que as crises epilépticas podem induzir a geração de um ciclo vicioso entre neuroinflamação e apoptose celular, induzindo ao estresse oxidativo e resultando no dano ao DNA nos pacientes com epilepsia. Além disso, nós sugerimos que o uso de FAEs que atuem na via do TNF-α ou IFN-لا poderia representar uma terapia complementar no tratamento dos pacientes epilépticos.
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Koskenkorva, Taija Susanna. "Insights into the function of Pseudomonas aeruginosa flavohemoglobin : identification of regulatory factors and their roles in the transcription of fhp during nitrosative and oxidative stress /." Zürich : ETH, 2007. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17211.
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Möllsten, Anna. "Factors influencing the risk of diabetic nephropathy : analyses of genes, smoking and diet." Doctoral thesis, Umeå universitet, Pediatrik, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-911.
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Diabetic long-term complications, despite intensive treatment, cause serious handicaps at relatively young age in diabetic patients. Diabetic nephropathy (DN) develops in up to 30% of patients with type 1 diabetes (T1D). Besides the eventual loss of kidney function, with need for dialysis treatment and transplantation, this complication also increases the risk of early death from cardiovascular disease. In addition to hyperglycaemia, the risk of developing DN is influenced by a number of life-style related factors, such as smoking and diet, but the mechanisms of action of these factors are largely unknown. The incidence of DN is not linearly related to diabetes duration. There is a peak incidence of DN at 15-20 years and this, together with results from family studies, shows that genetic factors are important contributors. Possible candidate genes are those involved in regulation of intraglomerular pressure and blood pressure, oxidative stress and inflammation. The main aims of this thesis were: ● To investigate the risk of DN associated with polymorphisms in; A) the endothelial NO-synthase gene (NOS3) and genes in the renin-angiotensin-system (RAAS) (all involved in the regulation of intraglomerular pressure). B) the manganese superoxide dismutase gene (SOD2) (involved in the regulation of oxidative stress). C) the ICAM1 gene (involved in activation and migration of lymphocytes) ● To investigate gene-smoking interactions ● To investigate the influence of normal diet on risk of microalbuminuria. The aims were addressed in different case-control settings, including 347 T1D patients from Sweden and 1163 patients from Finland, with or without DN, defined as; overt DN – having albumin excretion rate (AER) ≥200 μg/min, incipient DN – AER between 20 and 200 μg/min, non-DN controls – having AER <20 μg/min and at least 20 years of diabetes duration. In one study also non-diabetic healthy individuals were included to asses the risk of T1D associated with the ICAM1 gene. Results: The RAAS genes were investigated in the Swedish sample set and there was an association between a polymorphism in the angiotensin II type 1 receptor (AGTR1) gene and overt DN, when adjusting for age, duration of diabetes, HbA1c, sex and smoking (adjusted OR=3.04, 99% CI=1.02-9.06). Also a synergistic interaction with smoking was indicated. The ICAM1 gene was investigated in the Swedish sample set, but no association with DN was found. There were, however, associations between T1D and two polymorphisms in this gene, rs281432 (OR=1.64, 95% CI=1.14-2.38) and rs5498 (OR=2.46, 95% CI=1.59-3.80). In the combined Swedish/Finnish sample set, the Glu/Glu genotype of the Glu298Asp polymorphism in the NOS3 gene was associated with DN when age at diabetes onset, duration of diabetes, HbA1c, blood pressure, sex and smoking were taken into account (adjusted OR=1.46, 95% CI=1.12-1.91). There was also association between a polymorphism in the MnSOD gene and DN in this sample set. Homozygosity for the valine-allele of the Val16Ala polymorphism was associated with increased risk of DN in a model including age at diabetes onset, duration of diabetes, HbA1c, sex and smoking (adjusted OR=1.32, 95% CI=1.00-1.74). Smoking was associated with DN (OR=2.00, 95% CI=1.60-2.50) and in the Swedish sample set there were indications of interactions between smoking and the NOS3 and SOD2 genes, but these results could not be confirmed in the Finnish sample set. A high protein intake can enhance glomerular filtration rate and accelerate progression to DN, also other dietary components such as fat, fibres, vitamins and the ratio red/white meat have been discussed as important for DN development. In a nested case-control study including young T1D patients, the normal dietary intakes of protein and other nutrients were assessed using a semiquantitative questionnaire. The results showed that T1D patients consuming more than 6.5 g fish protein (>75th percentile) per day were at slightly lower risk to have microalbuminuria in both crude (OR=0.49, 95% CI=0.25-0.97) and adjusted analyses (OR=0.26, 95% CI=0.09-0.76, adjusted for age, duration of diabetes, sex, HbA1c, mean arterial pressure, BMI, region, smoking, energy intake and fish fat intake). Conclusions: The risk of having diabetic nephropathy is influenced by at least two genes controlling blood pressure and one gene protecting against oxidative stress. Smoking also increases the risk of DN and our findings indicate that smoking may accentuate the effect of the AGTR1, NOS3 and SOD2 genes. Normal dietary intake of protein was not associated with risk of having microalbuminuria in young T1D patients, on the other hand, an intake of fish protein above the 75th percentile decreased the risk of microalbuminuria.
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Permuth, Wey Jennifer. "Evaluation of Common Inherited Variants in Mitochondrial-Related and MicroRNA-Related Genes as Novel Risk Factors for Ovarian Cancer." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3488.
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Epithelial ovarian cancer (EOC) is a leading cause of morbidity and mortality among women in the United States, and the etiology is incompletely understood. Common, low penetrant genetic variants such as single nucleotide polymorphisms (SNPs) likely contribute to a significant proportion of EOC. We examined whether SNPs in two understudied yet biologically important types of genes, mitochondrial-related and miRNA-related genes, may contribute to EOC susceptibility using data from a large, homogeneous study population of 1,815 EOC cases and 1,900 controls (frequency-matched on age-group and race/ethnicity) genotyped through stage 1 of an ongoing genome-wide association study. Inter-individual variation in genes involved in mitochondrial biogenesis was strongly associated with EOC risk (empirical P=0.050), especially for genes NRF1, PPARGC1A, MTERF, ESRRA, and CAMK2D. SNPs in several genes involved in the biogenesis of miRNAs (LIN28, LIN28B, AGO2, DICER, and DROSHA) also demonstrated associations with EOC risk; a joint meta-analysis and in vitro investigations reinforced evidence for a protective role of LIN28B rs12194974 (combined OR= 0.90, 95% CI: 0.82-0.98), a G>A SNP predicted to reside in a transcription factor binding site in the highly conserved LIN28B promoter. Our findings provide valuable insight into the pathogenesis of EOC, and support the consideration of variants in these genes as candidates when building risk prediction models. Most importantly, this work has provided a strong foundation for further lines of research that may aid in reducing the burden of this disease.
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Mello, Maristela Previato. "Caracterização funcional de fatores de transcrição da família MarR de Chromobacterium violaceum." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17136/tde-13092018-104909/.
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Os fatores de transcrição da família MarR atuam como sensores diretos de sinais intracelulares e regulam vários processos em bactérias, incluindo virulência e degradação de compostos aromáticos. Neste trabalho, identificamos de modo global os fatores de transcrição da família MarR envolvidos na virulência do patógeno oportunista de humanos Chromobacterium violaceum. Usando mutagênese por troca alélica, geramos mutantes nulos não polares para doze dos quinze reguladores da família MarR encontrados no genoma de C. violaceum. Em ensaios de virulência, quando injetados por via intraperitoneal em camundongos BALB/c, os mutantes ?CV_0210 (?ohrR), ?CV_0577 e ?CV_2726 foram menos virulentos, enquanto o mutante ?CV_1776 foi mais virulento, quando comparados à linhagem selvagem. Para os demais nove mutantes MarR não houve diferença na virulência. Para definir o regulon de alguns destes reguladores da família MarR, os perfis de expressão gênica foram determinados por ensaios de microarranjo de DNA e Northern blot para as linhagens mutantes ?CV_0210 (?ohrR), ?CV_1776, ?CV_1810 e ?CV_2726, para a linhagem selvagem superexpressando CV_2726 e para a linhagem selvagem em estresse oxidativo com hidroperóxido de cumeno (CHP). O regulon do repressor CV_1810 compreendeu dois operons divergentes, que codificam enzimas que possivelmente metabolizam compostos aromáticos, mas produtos do catabolismo destes compostos não funcionaram como ligantes capazes de antagonizar a repressão de CV_1810 no gene CV_1801. O regulon do ativador CV_2726, definido como quatorze genes comuns diferencialmente expressos em ensaios na ausência e na condição de superexpressão do gene CV_2726, revelou poucos genes (cstA) com potencial de estar envolvidos no fenótipo de menor virulência do mutante ?CV_2726. Os reguladores CV_0577 e CV_1776 foram alocados na subfamília UrtR de resposta a urato e provavelmente influenciam a virulência de C. violaceum com regulons sobrepostos. O regulon de CV_1776 abrangeu dezenas de genes, muitos deles relacionados ao catabolismo de aminoácidos, mas há poucos candidatos a fatores de 10 virulência clássicos (pecM, escU). Alguns genes do catabolismo/utilização de purinas (CV_0578 e CV_3771) foram regulados tanto por CV_1776 quanto por CV_0577 e responderam a presença de urato. O perfil transcricional da resposta adaptativa de C. violaceum a CHP, um ligante que oxida o regulador OhrR, revelou aumento na expressão de genes relacionados à detoxificação de peróxidos (enzimas antioxidantes e sistemas redutores de tiol), degradação da porção aromática do CHP (oxigenases) e proteção contra estresses secundários (reparo de DNA, choque térmico, limitação de ferro e nitrogênio). O regulon de OhrR revelou-se pequeno, incluindo dois genes com expressão aumentada, CV_0209 (ohrA) e CV_0208 (possível diguanilato ciclase), e três genes com expressão diminuída (hemolisina, quitinase e colagenase) no mutante ?ohrR. Assim, a virulência atenuada do mutante ?ohrR deve estar relacionada ao aumento da produção do segundo mensageiro cíclico di-GMP (c-diGMP) e à diminuição da expressão de enzimas degradativas extracelulares. Em conclusão, definimos a resposta transcricional à CHP, identificamos potenciais fatores de virulência, como a diguanilato ciclase, no regulon OhrR, e mostramos que C. violaceum utiliza os fatores de transcrição da família MarR CV_0577, CV_1776, CV_2726 e OhrR para modular sua virulência.Transcription factors belonging to the MarR family act as direct intracellular sensors of signals and control many processes in bacteria, including virulence and degradation of aromatic compounds. In this work, we identify and characterize MarR family transcription factors controlling virulence in Chromobacterium violaceum, an opportunistic pathogen of humans. Using allelic exchange mutagenesis, we generate non-polar null mutants for twelve of the fifteen MarR family regulators found in the C. violaceum genome. In virulence tests, when introduced by intraperitoneal injection in BALB/c mice, the ?CV_0210 (?ohrR), ?CV_0577 and ?CV_2726 mutant strains were less virulent, while the ?CV_1776 was more virulent, when compared to the wild-type strain. The other nine MarR mutants showed no difference in virulence tests. To define the regulon of some MarR family transcription factors, the gene expression profiles were determined by DNA microarray analysis and Northern blot assays for the ?CV_0210 (?ohrR), ?CV_1776, ?CV_1810 and ?CV_2726 mutant strains, for the wild-type strain overexpressing CV_2726 and for the wild-type strain exposed to oxidative stress generated by cumene hydroperoxide (CHP). The CV_1810 is a repressor of a regulon that comprised two divergent operons encoding enzymes that possibly metabolize aromatic compounds, but catabolic products of these compounds did not function as ligands capable of antagonizing the repression of CV_1810 on the CV_1801 gene. The regulon of the activator CV_2726, defined as fourteen differentially expressed genes commonly found in assays in the absence and overexpression of the CV_2726 gene, revealed few genes (cstA) with potential to be involved in the phenotype of lower virulence of the ?CV_2726 mutant strain. Regulators CV_0577 and CV_1776 were allocated in the urate-responsive UrtR subfamily and probably afect the virulence of C. violaceum with overlapping regulons. The CV_1776 regulon contains dozens of genes, many of them related to amino acid catabolism, but there are few candidates for classical virulence factors (pecM, escU). Some genes related to catabolism/utilization of purine (CV_0578 and CV_3771) were 12 regulated by both CV_1776 and CV_0577 and responded to the presence of urate. The transcriptional profile of the adaptive response of C. violaceum to CHP, a ligand that oxidizes the OhrR regulator, revealed the upregulation of genes related to the detoxification of peroxides (antioxidant enzymes and thiol-reducing systems), degradation of the aromatic moiety of CHP (oxygenases), and protection against other secondary stresses (DNA repair, heat shock, iron limitation, and nitrogen starvation responses). The OhrR regulon was shown to be small, including two upregulated genes, CV_0209 (ohrA) and CV_0208 (putative diguanylate cyclase), and three downregulated genes (hemolysin, chitinase, and collagenase) in the ?ohrR mutant. Thus, the attenuated virulence of the ?ohrR mutant might be related to the increased production of the second messenger cyclic di-GMP (c-di-GMP) and the decreased expression of extracellular enzymes required for tissue dissemination, in this mutant strain. In conclusion, we have defined the transcriptional response to CHP, identified potential virulence factors such as diguanylate cyclase as members of the OhrR regulon, and shown that C. violaceum uses the transcription factors of the MarR family CV_0577, CV_1776, CV_2726 and OhrR to modulate its virulence.
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Silva, Ana Luísa Patrício. "Impact of natural and/or chemical stressors on the freeze-tolerant and euryhaline enchytraeid, Enchytraeus albidus." Doctoral thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/16009.
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Doutoramento em BiologiaRapid climatic changes are taking place in Arctic, subarctic and cold temperate regions, where predictions point to an increase in freeze-thaw events, changes in precipitation, evaporation and salinity patterns. Climate change may therefore result in large impacts in ecosystem functioning and dynamics, especially in the presence of contaminants due to intense anthropogenic activities. Even though multiple stress approaches have received increasing interest in the last decades, the number of such studies is limited. In particular, knowledge on the effect of freezethaw events and salinity fluctuations on ecotoxicology of soil invertebrates is lacking, especially important when considering supralittoral species. Therefore, the aim of this thesis was to investigate the effects of low temperature and salinity fluctuations, singly and in combination with contaminants, in the freeze-tolerant and euryhaline enchytraeid Enchytraeus albidus. The assessment of population level endpoints (survival and reproduction), along with physiological and biochemical parameters such as levels of cryoprotectants, ice/water content, oxidative stress biomarkers, cellular energy allocation, and tissue concentration of chemicals (when applied), provided new and valuable knowledge on the effects of selected physical and chemical stressors in E. albidus, and allowed the understanding of adjustments in the primary response mechanisms that enable worms to maintain homeostasis and survival in harsh environments such as polar and temperate-cold regions. The presence of moderate levels of salinity significantly increased freeze-tolerance (mainly evaluated as survival, cryoprotection and ice fraction) and reproduction of E. albidus. Moreover, it contributed to the readjustments of cryoprotectant levels, restoration of antioxidant levels and changed singnificantly the effect and uptake of chemicals (copper cadmium, carbendazim and 4-nonylphenol). Temperature fluctuations (simulated as daily freeze-thaw cycles, between -2ºC and -4ºC) caused substancial negative effect on survival of worms previsouly exposed to non-lethal concentrations of 4-nonylphenol, as compared with constant freezing (-4ºC) and control temperature (2ºC). The decrease in cryoprotectants, increase in energy consumption and the highest concentration of 4-nonylphenol in the tissues have highlighted the high energy requirements and level of toxicity experienced by worms exposed to the combined effect of contaminants and freezing-thawing events. The findings reported on this thesis demonstrate that natural (physical) and chemical stressors, singly or in combination, may alter the dynamics of E. albidus, affecting not only their survival and reproduction (and consequent presence/distribution) but also their physiological and biochemical adaptations. These alterations may lead to severe consequences for the functioning of the ecosystems along the Arctic, subarctic and cold temperate regions, where they play an important role for decomposition of dead organic matter. This thesis provides a scientific basis for improving the setting of safety factors for natural soil ecosystems, and to underline the integration of similar investigations in ecotoxicology, and eventually in risk assessment of contaminants.
As alterações climáticas estão a atingir rapidamente as regiões do Ártico, SubÁrtico e as regiões temperadas, apontando as previsões para um aumento de eventos de congelamento-descongelamento, bem como mudanças nos padrões de precipitação, evaporação e de salinidade. Estas alterações climáticas poderão resultar em impactos francamente negativos no funcionamento e dinâmica de ecossistemas, especialmente quando associados à presença de contaminantes resultantes da intensa atividade antropogénica. Embora a incorporação de stressores múltiplos em estudos de ecotoxicidade tenha recebido um crescente interesse pela comunidade científica, o seu número é ainda reduzido. Particularizando, o conhecimento dos efeitos de eventos de congelamento-descongelamento e de flutuações de salinidade permanecem desconhecidos, especialmente quando se consideram espécies supra-litorais. Neste contexto, o objetivo geral da presente tese consistiu em investigar os efeitos das flutuações de temperaturas e salinidade, individualmente ou em combinação com contaminantes, no enquitraídeo tolerante ao frio e eurialino - o Enchytraeus albidus. A avaliação de parâmetros populacionais (sobrevivência, reprodução e bioacumulação), fisiológicos (níveis de crioprotetores, conteúdo em gelo / água, temperatura de fusão e sobrecongelamento) e bioquímicos (biomarcadores de stress oxidativo, alocação de energia celular) permitiu compilar novas e valiosas informações sobre os efeitos dos stressores físicos e químicos selecionados no enquitraídeo e compreender quais os reajustes nos mecanismos de resposta primários que lhes permitem manter a homeostasia e sobrevivência em ambientes inóspitos como as regiões Polares e temperadas-frias. A presença de níveis moderados de salinidade aumentou significativamente a tolerância a temperaturas congelantes (essencialmente avaliada como sobrevivência, crioprotecção e fracção de gelo extracelular) e a reprodução do E. albidus. Além disso, contribuiu para a regulação de crioprotectores, restauração dos níveis de antioxidantes nestes organismos e alterou significativamente o efeito e a incorporação/absorção de substâncias químicas (cádmio, cobre carbendazim e 4-nonilfenol). As flutuações de temperatura (simuladas como ciclos diários de congelamento-descongelamento, com temperaturas entre 2ºC e -4ºC) causaram um efeito substancialmente negativo na sobrevivência de organismos previamente expostos a concentrações não letais de 4-nonilfenol, quando comparados com organismos expostos a uma temperatura congelante constante (-4ºC) ou à temperatura controlo (2ºC). A diminuição na crioproteção, o aumento no consumo de energia e a maior concentração de 4-nonilfenol nos tecidos vieram sublinhar o elevado gasto energético e o nível de toxicidade sofrido pelos organismos expostos à combinação de contaminantes e eventos de congelamento e descongelamento. Os resultados apresentados nesta tese demonstram, assim, que a presença de stressores naturais (físicos) e químicos, isoladamente ou em combinação, podem alterar a dinâmica do E. albidus, afetando não só a sua sobrevivência e reprodução (e consequente presença / distribuição), mas também as suas adaptações fisiológicas e bioquímicas. Essas alterações podem levar a consequências graves para o funcionamento dos ecossistemas do Ártico, subÁrtico e regiões temperadas-frias, uma vez que estes organismos desempenham um papel importante para a decomposição de matéria orgânica morta. Esta tese fornece ainda uma base científica para melhorar a atribuição de coeficientes de segurança para os ecossistemas naturais do solo, alertando para a integração de investigações semelhantes em ecotoxicologia, e, eventualmente, para a avaliação de risco ecológico de contaminantes.
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Liu, Beiqing. "Distinct regulation of early gene transactivation and IL-2 gene expression by sublethal levels of oxidative stress in activated human T lymphocytes: Involvement of intracellular signaling pathways and transcription factors /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487945015617244.
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Vanzella, Cláudia. "Efeitos do exercício físico sobre a memória e sobre parâmetros bioquímicos e moleculares no hipocampo e no músculo de ratos senescentes." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/158166.
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O envelhecimento é um processo no qual ocorrem alterações estruturais e funcionais da maioria dos órgãos, que podem levar ao aumento da susceptibilidade a várias doenças associadas à idade. Assim, várias estratégias têm sido investigadas a fim de se reduzir os sintomas relacionados à idade e o exercício físico tem demonstrado efeito neuroprotetor em diferentes modelos experimentais. Nesta tese, investigamos os efeitos do exercício físico moderado sobre a memória e sobre parâmetros bioquímicos no hipocampo e no músculo sóleo de ratos Wistar de 3, 6 e 22 meses de idade. Para isso, foram realizados três experimentos distintos que deram origem aos três capítulos apresentados na tese. No primeiro experimento, estudamos o efeito do exercício físico em ratos de 3 e 22 meses de idade. Neste experimento, o exercício preveniu o déficit de aquisição da memória de referência relacionado à idade. Além disso, preveniu o aumento do estresse oxidativo no hipocampo de ratos envelhecidos e também promoveu o aumento da expressão dos fatores neurotróficos BDNF, NT-3 e IGF-1 no hipocampo destes animais. É importante ressaltar que houve uma correlação positiva entre a redução do estresse oxidativo e a latência para encontrar a plataforma no 5º dia de treino na tarefa de memória de referência, ou seja, a redução do conteúdo de espécies reativas e da lipoperoxidação pelo exercício está correlacionada com a melhora do desempenho de memória dos ratos envelhecidos. No segundo experimento, avaliamos o efeito do exercício físico em ratos de 3, 6 e 22 meses de idade. Corroborando com os resultados apresentados no experimento anterior, foi demonstrado que o exercício físico moderado preveniu os déficits de memória espacial de referência e de trabalho relacionados à idade. O treinamento cognitivo no Water maze aumentou a atividade das enzimas Na+,K+- ATPase e AChE no hipocampo de ratos adultos e envelhecidos. O aumento na atividade da Na+,K+-ATPase foi ainda maior nos ratos envelhecidos submetidos ao exercício físico combinado com o treinamento cognitivo. Além disso, foi observada uma correlação positiva entre a atividade da Na+,K+-ATPase no hipocampo dos ratos envelhecidos exercitados e a latência para encontrar a plataforma no 5º dia de treino na tarefa de memória de referência, ou seja, o aumento da atividade da Na+,K+-ATPase está associado com a melhora do desempenho de memória relacionado ao exercício físico. De acordo com esses dados, também foi observada uma correlação negativa entre a atividade da Na+,K+-ATPase e a diferença (delta) entre a média das latências entre os trials 1 e 4 na tarefa de memória de trabalho, o que demonstra que os ratos envelhecidos exercitados apresentaram um melhor desempenho na tarefa de memória de trabalho associado com o aumento na atividade da Na+,K+-ATPase. No terceiro experimento, investigamos o efeito do exercício físico em ratos de 3 e 22 meses de idade. O exercício aumentou o conteúdo de espécies reativas e a lipoperoxidação no músculo sóleo de ratos jovens. Ratos envelhecidos apresentaram um aumento da lipoperoxidação e uma redução na atividade da enzima catalase. O exercício induziu um aumento dos níveis de espécies reativas, uma redução no conteúdo de sulfidrilas e o aumento de proteínas carboniladas; contudo, promoveu o aumento da atividade das enzimas superóxido dismutase e catalase no sóleo dos ratos envelhecidos. Assim, os resultados do primeiro e do segundo experimento demonstram que o exercício físico preveniu o declínio da memória espacial relacionado à idade e que esse efeito pode ser mediado por fatores que incluem a redução do estresse oxidativo, o aumento da expressão de fatores neurotróficos e o aumento da atividade da enzima Na+,K+-ATPase no hipocampo de ratos envelhecidos. Os resultados do músculo demonstram que o sóleo dos ratos jovens, embora susceptível ao aumento das espécies reativas e lipoperoxidação, não apresentou dano às proteínas, sugerindo que outros mecanismos, como o sistema de defesa antioxidante não enzimático, possam estar atuando para compensar os efeitos do exercício. Além disso, o músculo dos ratos envelhecidos parece ser mais sensível que o dos ratos jovens às alterações do estado oxidativo celular induzidas pelo exercício físico, porque apesar dos animais envelhecidos exercitados apresentarem um aumento na atividade das enzimas antioxidantes, não houve uma redução do dano oxidativo.Aging is a process in which structural and functional changes occur in most organs and may lead to increased susceptibility to various age-related diseases. Several approaches have been investigated with the aim of reducing age-related symptoms and physical exercise is a therapeutic strategy that has presented neuroprotective action in different experimental models. In this context, some studies show that regular physical exercise is related to the improvement of quality of life and to the prevention of age-related cognitive decline. In the present thesis, we investigated the effect of moderate physical exercise on memory and on biochemical parameters in the hippocampus and soleus muscle in 3, 6 and 22 months-old rats. For that, three different experiments were carried out, which gave rise to the three chapters presented in this thesis. In the first experiment, we studied the effect of physical exercise in 3 and 22 months-old rats. In this experiment, the exercise prevented the age-related acquisition deficit of reference memory. In addition, exercise prevented the increased in oxidative stress and also was able to increase the expression of neurotrophic factors BDNF, NT-3 and IGF-1 in the hippocampus of aged rats. It is important to note that there was a positive correlation between the reduction of oxidative stress and latency to find the platform on the 5th day of training in the reference memory task, i.e., reduction of reactive species levels and lipid peroxidation, might be associated with the exercise-related memory improvement. In the second experiment, we evaluated the effect of physical exercise in 3, 6 and 22 months-old rats. Corroborating with the results presented in the previous experiment, it was demonstrated that moderate physical exercise prevented age-related spatial reference and working memory deficits. It has also been shown that the cognitive training in Water maze increased the activity of the Na+,K+-ATPase and AChE enzymes in the hippocampus of adult and aged rats. The increase in Na+,K+-ATPase activity was even further increased in aged rats that were submitted to physical exercise combined with cognitive training. In addition, a positive correlation was observed between the Na+,K+-ATPase activity in the hippocampus of aged exercised rats and the latency to find the platform on the 5th day of training in the reference memory task, i.e., the increase in Na+,K+-ATPase activity is associated with the exercise-related memory improvement in aged rats. Consistently, a negative correlation between the Na+,K+-ATPase activity and the difference (delta) between the mean latencies of trials 1 and 4 in the working memory task was also found, i.e., the exercised aged rats showed better performance in the working memory task associated with the increase in Na+,K+-ATPase activity. In the third experiment, we investigated the effect of physical exercise in 3 and 22 months-old rats. Exercise increased the reactive species content and lipid peroxidation in soleus muscle of young rats. Aged rats showed an increase in lipid peroxidation and a reduction in the catalase activity. Exercise induced an increase in reactive species levels, a reduction in sulfhydryl content and an increase in carbonyl proteins; however, the exercise was able to increase the superoxide dismutase and catalase activities in the soleus of aged rats. Thus, the results of first and second experiments demonstrate that physical exercise prevents the age-related decline of spatial memory and this effect might be related to the reduction of oxidative stress, increased expression of neurotrophic factors and the increase in the Na+,K+-ATPase activity in the hippocampus of aged rats. The muscle results demonstrate that soleus of young rats, although susceptible to the increased in reactive species and lipid peroxidation, showed no damage to proteins, suggesting that other mechanisms, such as the non-enzymatic antioxidant defense system, may be acting to compensate the effects of exercise. In addition, the muscle of the aged rats seems to be more sensitive than the young rats to changes in the cellular oxidative state induced by exercise, since aged exercised animals showed an increase in the activity of antioxidant enzymes, but there was no reduction of oxidative damage.
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Juvany, Cánovas Marta. "Edat cronològica, edat fisiològica i sexe: factors determinants de l'estrès oxidatiu en plantes." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/283933.
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Els processos metabòlics en plantes, com ara la fotosíntesi, la fotorespiració i la respiració, comporten l’inevitable producció d’espècies reactives de l’oxigen (ROS) en cloroplasts, peroxisomes i mitocondris. En determinades concentracions les ROS poden actuar com a molècules implicades en la senyalització cel•lular, però degut a la seva elevada reactivitat, un augment de les ROS provoca l’oxidació de components cel•lulars alterant-ne la seva funció biològica i provocant dany oxidatiu a la planta. En condicions d’estrès, tant biòtic com abiòtic, les plantes experimenten un increment dels nivells de ROS. Per tal de mantenir l’homeòstasi redox, aquestes han desenvolupat un seguit de mecanismes antioxidants capaços de reduir els nivells de ROS evitant un possible dany oxidatiu. La recerca per desxifrar les respostes de les plantes a l’estrès ha anat en augment en els últims anys, però encara avui en dia és poc el coneixement que tenim sobre els mecanismes implicats en el cas de les plantes perennes, tot i que constitueixen una part molt important del regne vegetal. Per altra banda, tot i l’evident importància de l’estrès oxidatiu, són escassos els estudis que s’han plantejat com aquest es pot veure afectat per factors intrínsecs de la planta, com l’edat o el sexe. L’objectiu principal d’aquesta tesi ha estat determinar com l’edat de la planta, tant la cronològica com la fisiològica, i el sexe poden influir en l’estrès oxidatiu en plantes perennes. L’anàlisi del nivells d’estrès oxidatiu es va dur a terme mitjançant les mesures de diferents mecanismes antioxidants com els carotenoides, l’alfa-tocoferol i els antocians, però centrant-nos sobretot en el paper de l’àcid malondialdehid, un subproducte de la peroxidació lipídica. Els estudis es van realitzar en fulles i plantes juvenils de Pistacia lentiscus L., una espècie dioica i perenne típica del clima mediterrani, i en arbres moribunds de Fagus sylvatica L., proporcionant un bon model a causa de la seva avançada edat, tant cronològica com fisiològica. Els resultats obtinguts revelen que l’augment dels nivells de peroxidació lipídica com a indicador d’estrès oxidatiu pot significar un dany o un possible mecanisme de senyalització interna; per això, la consideració conjunta de l’edat cronològica i els nivells d’estrès oxidatiu és un bon indicador de l’edat fisiològica, tant a nivell de fulla com de planta sencera. L’esforç reproductiu en plantes dioiques ocasiona canvis en els mecanismes fotoprotectors en les femelles respecte als mascles en condicions ambientals adverses. Tot i que les femelles presenten uns nivells d’estrès oxidatiu superiors als dels mascles, no es veuen afectades negativament, el que suggereix un possible rol en senyalització. Així mateix, l’estudi a nivell modular mitjançant la comparació entre brots reproductius i no reproductius en femelles va revelar una major fotoprotecció en els brots reproductius, com indicaven els nivells d’antioxidants i la major dissipació d’excés d’energia en forma de calor, emfatitzant la importància de la diferenciació entre mòduls en l’estudi de les diferències entre sexes en plantes dioiques.Metabolic processes in plants such as photosynthesis, photorespiration and respiration, produce reactive oxygen species (ROS). ROS are highly toxic molecules but besides of its damaging nature they are implicated in cell signaling in different cellular processes. However, under stress conditions plants can suffer an increase of ROS levels. When ROS concentration becomes high enough to overwhelm antioxidant systems, plant suffer oxidative stress as a consequence of the unbalanced cellular redox status. Despite the importance to unravel plant stress responses, little is known about the mechanisms implicated in perennial plants. Furthermore, the possible effect of plant intrinsic factors, as plant age or reproductive effort, in oxidative stress levels is still poorly understood. The main objective of this thesis was to determine how plant age, both chronological and physiological, as well as reproductive effort may influence oxidative stress levels in perennial plants. With this purpose levels of antioxidants as carotenoids, anthocyanins and alpha-tocopherol together with endogenous contents of stress hormones were measured, but with special emphasis in malondialdehyde acid levels, a byproduct of lipid peroxidation. To better understand the plant age effect we used leaves and juvenile plants of Pistacia lentiscus as well as moribund beech trees. Increases in lipid peroxidation not only could mean an oxidative damage but play a signaling role. Therefore, chronolorgical age concomitantly with the measure of oxidative stress levels is a good indicator of plant physiological age. Sex-related changes in photoprotection mechanisms between female and male plants of Pistacia lentiscus, a dioecious plant, where observed under climatological adverse conditions. Although females phowed higher oxidative stress levels compared to males, females were not affected negatively, suggesting a role in signaling. In addition, photoprotection capacity was higher in reproductive shoots relative to non-reproductive shoots in females, thus suggesting that females prioritized protection to fruit-bearing shoots.
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Ingelsson, Erik. "Insulin Resistance and Inflammation as Risk Factors for Congestive Heart Failure." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5879.
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Tomás, Mestres Marta. "Factors genètics i ambientals i les seves interaccions com a determinants de l'efecte protector de la paraoxanasa1 en la malaltia cardiovascular." Doctoral thesis, Universitat Pompeu Fabra, 2003. http://hdl.handle.net/10803/7067.
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La present tesi avalua els efectes de certs factors ambientals sobre la paraoxonasa1 (PON1), enzim antioxidant, possiblement protector enfront les malalties cardiovasculars, a través de dos estudis d'intervenció i un de transversal. En primer lloc, el tractament amb simvastatina dels pacients amb hipercolesterolèmia familiar, que presentaven una activitat paraoxonasa baixa, s'associava a un increment de l'activitat fins a valors similars als d'individus normolipèmics, independentment dels polimorfismes PON1-55 o PON1-192. En segon lloc, l'entrenament físic s'associava a un augment de l'activitat paraoxonasa en els individus QQ i una disminució de la mateixa en els portadors de l'al·lel R pel polimorfisme PON1-192. L'increment de l'activitat paraoxonasa immediatament després de l'exercici físic agut era seguit per una disminució subseqüent de l'activitat. La recuperació dels nivells basals d'activitat paraoxonasa a les 24h de l'exercici físic agut es donava en els individus QQ independentment del seu estat d'entrenament, i en els individus portadors de l'al·lel R només quan estan entrenats. En tercer lloc, el consum elevat d'àcid oleic comportava un augment de la concentració de c-HDL i de l'activitat paraoxonasa en els homes portadors dels genotips QR i RR del polimorfisme PON1-192, respectivament.Paraules claus: paraoxonasa, PON1, genotips, simvastatina, hipercolesterolèmia familiar, interacció gen-dieta, lipoproteïna d'alta densitat (HDL), exercici físic agut, entrenament físic, estrès oxidatiu, àcid oleic, oli d'oliva, peròxids lipídics, malaltia cardiovascular.
The present thesis evaluates some environmental factor effects on paraoxonase1 (PON1), an possibly protective against cardiovascular disease antioxidant enzyme, through two intervention studies and a cross-sectional one. First, treatment with simvastatin of the familial hypercholesterolemic patients, which had low paraoxonase activity, was associated with an increase in the activity to values similar to the normolipemic ones, regardless of the PON1-55 or PON1-192 polymorphisms. Second, Regular exercise was associated with an increase in PON1 activity in QQ subjects and with a decrease in R carriers. Increased PON1 activity immediately after a bout of exercise was subsequently followed by a decrease of activity. The recovery of the basal PON1 activity levels at 24 h was found in QQ subjects regardless of their training status and in trained R carriers, but not in untrained R carriers.
Third, high oleic acid intake was associated with increased HDL cholesterol and PON1 activity levels only in men who were QR and RR of the PON1-192 polymorphism, respectively.
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Pasanen, A. K. (Anna Kaisa). "A translational study on the roles of redox molecules, cell cycle regulators and chemokine receptors as prognostic factors in diffuse large B-cell lymphoma." Doctoral thesis, Oulun yliopisto, 2013. http://urn.fi/urn:isbn:9789526202624.
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Abstract Lymphomas are a group of more than 70 different malignancies arising from lymphoid tissues and diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma. More than 70% of DLBCL patients can be cured with modern therapy, but some patients still die of the disease. The recognition of patients with adverse prognosis, justifying deviation from standard treatment and risking severe side effects, is problematic. The aim of this study was to identify potential biological factors for the prediction of poor treatment response and central nervous system (CNS) relapse in DLBCL patients. The study included 263 lymphoma patients. 205 patients had a DLBCL, and 37 of these represented primary CNS lymphoma (PCNSL). Immunohistochemistry was used to determine the expression of oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine, as well as antioxidant enzymes manganese superoxide dismutase (MnSOD), thioredoxin (Trx) and gamma cysteine ligase (GCL) from samples representing reactive lymphoid tissue and B-cell derived lymphomas. From DLBCL samples staining was also conducted for cell cycle regulating proteins p16, p53, p21 and p27 and chemokine receptors CXCR4, CXCR5 and CCR7. Immunoelectron microscopy (IEM) for CXCR4 and CXCR5, and their ligands CXCL12 and CXCL13 was performed on additional samples from reactive lymphoid tissue, nodal DLBCL, secondary CNS lymphoma and PCNSL. Factors associated with adverse prognosis included expression of nitrotyrosine, Trx and GCL. A prognostic score reflecting the degree of cell cycle dysregulation within each patient’s tumour identified 3 distinct prognostic groups among DLBCL patients. High cytoplasmic CXCR5 expression was associated with CNS involvement, whereas nuclear CXCR4 expression correlated with nodal disease. These results demonstrate the considerable biological heterogeneity seen within DLBCL, but further research is needed to confirm them. High antioxidant activity and the accumulation of damage to cell cycle regulating pathways separated patient groups with a poor prognosis that might benefit from new types of treatment. Chemokine receptor expression seems to play a role in the CNS tropism of DLBCL, and, if confirmed, could in the future contribute to more effective targeting of CNS prophylactic therapiesTiivistelmä Lymfoomat ovat yli 70 erilaisen maligniteetin muodostama ryhmä imukudoksen syöpiä, ja diffuusi suurisoluinen B-solulymfooma (engl. DLBCL) on yleisin lymfoomatyyppi. Yli 70 prosenttia DLBCL-potilaista pystytään parantamaan nykyaikaisilla hoidoilla, mutta osa potilaista kuolee edelleen tautiin. Nämä potilaat tarvitsisivat tehokkaampia hoitoja vakavien haittavaikutusten riskistä huolimatta, mutta huonon ennusteen potilaiden tunnistaminen etukäteen on vaikeaa. Tutkimuksen tavoitteena oli löytää biologisia tekijöitä DLBCL-potilaiden hoitovasteen ja taudin keskushermostossa (engl. CNS) uusiutumisen ennustamiseen. Aineisto sisältää 263 lymfoomapotilasta. 205 potilaalla on DLBCL, ja 37:llä näistä primaari aivolymfooma (PCNSL). Immunohistokemiallisilla värjäyksillä määritettiin oksidatiivisen stressin markkereiden 8-hydroksideoksiguanosiinin (8-OHdG) ja nitrotyrosiinin, sekä antioksidanttientsyymien mangaanisuperoksidi-dismutaasin (MnSOD), tioredoksiinin (Trx) ja gammakysteiiniligaasin (GCL) ilmentyminen reaktiivista imukudosta sekä B-soluperäisiä lymfoomia edustavissa näytteissä. DLBCL-näytteistä määritettiin lisäksi solusykliä säätelevien proteiinien p16, p53, p21 ja p27 sekä kemokiinireseptorien CXCR4, CXCR5 ja CCR7 ilmentyminen. Lisäksi reaktiivista imukudosta, imusolmuke-DLBCL:aa, sekundaarista CNS-lymfoomaa ja PCNSL:aa edustavista näytteistä määritettiin immunoelektronimikroskooppisesti reseptorien CXCR4 ja CXCR5 sekä ligandien CXCL12 ja CXCL13 ilmentyminen. Tulosten mukaan voimakas nitrotyrosiini-, Trx- ja GCL-positiivisuus ovat yhteydessä huonoon ennusteeseen. Solusyklin säätelyhäiriön vaikeusastetta kuvaava ennusteellinen pisteytys jaotteli DLBCL-potilaat kolmeen ennusteelliseen ryhmään. Runsas sytoplasminen CXCR5-positiivisuus oli yhteydessä CNS-tautiin, kun taas tumapositiivisuus CXCR4:lle korreloi imusolmuketautiin. Tutkimustulokset kuvaavat DLBCL:n merkittävää biologista heterogeenisyyttä, mutta tulosten varmistamiseksi tarvitaan lisää tutkimuksia. Korkea antioksidanttiaktiivisuus ja solusyklin säätelyhäiriöiden kasautuminen erottivat huonoennusteisia potilasryhmiä, jotka voisivat hyötyä uudenlaisista hoidoista. Kemokiinireseptorien ilmentyminen vaikuttaisi olevan yhteydessä DLBCL:n CNS-hakuisuuteen, ja tulosten varmistuessa ekspressioprofiilien analysointia voitaisiin tulevaisuudessa hyödyntää ennaltaehkäisevien hoitojen tehokkaammassa kohdentamisessa
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Bonarriba, Beltrán Carlo Rakso. "Litiasis de oxalato cálcico monohidrato papilar y de dihidrato: estudio comparativo de factores de riesgo." Doctoral thesis, Universitat de les Illes Balears, 2014. http://hdl.handle.net/10803/134501.
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El cálculo de oxalato cálcico monohidrato (COM) papilar puede iniciarse en una calcificación subepitelial de la papila renal. La formación de hidroxiapatita en la capa epitelial papilar puede llegar a ser el nido del cálculo COM papilar. En este trabajo se estudian a 60 pacientes con litiasis de oxalato cálcico, 30 con COM papilar y 30 con oxalato cálcico dihidrato (COD). El potencial redox fue más alto en el grupo COM papilar que en el grupo COD, sugiriendo un déficit en antioxidantes debido a un incremento de estrés oxidativo. El calcio urinario fue significativamente más alto en el grupo COD, mientras que el oxalato urinario fue más alto en el grupo COM, sugiriendo un alto grado de injuria oxidativa en las células renales. La evaluación de las dietas mostraron que ambos grupos consumieron bajas cantidades de productos ricos en fitatos. De las enfermedades asociadas a urolitiasis, la prevalencia de úlcera gastroduodenal difiere significativamente, siendo mayor en el grupo COM y sugiere que las lesiones epiteliales son comunes entre las úlceras gastroduodenales y la litiasis COM papilar. La prevalencia de Diabetes Mellitus tipo 2 fue mayor significativamente en el grupo COD frente al grupo COM papilar. La exposición ocupacional a productos citotóxicos ocurren en 47% del COM papilar frente al 27% del grupo COD, pero sin diferencias estadísticamente significativas. El síndrome metabólico ocurre en 23% del grupo COD frente al 3% del grupo COM papilar. Estos hallazgos indican que el estrés oxidativo esta asociado con una injuria al tejido papilar y este sería el origen de las calcificaciones intrapapilares. La continuación de este proceso es debido a moduladores y/o deficiencias en inhibidores de la cristalización. La identificación y eliminación de las causas de injuria pueden prevenir episodios recurrentes en pacientes con cálculos COM papilar.Calcium oxalate monohydrate (COM) papillary calculi can be initiated by subepithelial calcification of the renal papillae. Hydroxyapatite disruption of the papillary epithelial layer can become the nidus of a COM papillary calculus. This study evaluated the causes of papillary tissue calcifications in 60 patients with calcium oxalate lithiasis, 30 with COM papillary and 30 with calcium oxalate dihydrate (COD) calculi. Urinary redox potential was higher in the COM papillary than the COD group, suggesting that the former are more deficient in antioxidants due to increased oxidative stress. Urinary calcium was significantly higher in the COD group, whereas urinary oxalate was significantly higher in the COM group, suggesting a great degree of oxidative injury of renal cells.Evaluations of their diets showed that both groups consumed low amounts of phytate-rich products. Of diseases possibly associated with urolithiasis, the prevalence of gastroduodenal ulcer differed significantly, being higher in the COM group and suggesting that epithelial lesions are common to gastroduodenal ulcers and COM papillary renal stones. The prevalence of Diabetes Mellitus type 2 was higher significantly in the COD than the COM papillary group. Occupational exposure to cytotoxic products occurred in 47% of the COM and 27% of the COD group, but this difference was not statistically significant. Metabolic syndrome occurred in 23% of the COD and 3% of the COM papillary. These findings indicate that oxidative stress is associated with injury to papillary tissue and that this is the origin of intrapapillary calcifications. The continuation of this process is due to modulators and/or deficiencies in inhibitors of crystallization. Identifying and eliminating the causes of injury may prevent recurrent episodes in patients with papillary COM calculi.
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Byon, Chang Hyun. "Oxidative stress-stimulated vascular calcification." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2010r/byon.pdf.
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Pelletier, Laure. "Individual and environmental drivers of the foraging behaviour in a long-lived coastal seabird." Phd thesis, Université de Strasbourg, 2013. http://tel.archives-ouvertes.fr/tel-01023688.
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To study the impact of environmental changes in a coastal marine ecosystem, it is necessary to use indicator species. It is crucial to understand the foraging performances that proceed from environmental changes. The aim of my thesis was to examine the influence of intrinsic and extrinsic factors on the foraging activity of the little penguins (Eudyptula minor). The thermocline allowed birds to approach optimal behaviour. However, the thermocline is an unstable element. I did not find any effect of individual characteristics on their foraging behaviour and success. My work suggests that environmental conditions are major factors that will influence the behaviour of little penguins, allowing me to conclude that little penguins are good ecological indicators.
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Fairbrass, Danielle L. "Engineering oxidative stress resistance in CHO cell factories." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/16227/.
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Oxidative stress is a phenomenon created by an imbalance in the amount of Reactive Oxygen Species (ROS) created within a cell, and the ability of its defence mechanisms to effectively deal with ROS. Oxidative stress is extremely deleterious to the cell, and is known to cause damage to DNA, proteins and lipids (Turrens, 2003). Mitochondria are the cell’s predominant producer of ROS (Murphy, 2009), but it has also been shown that increased protein folding in the Endoplasmic Reticulum (ER) results in an increase in ROS levels (Malhotra, 2008), an issue particularly pertinent as developers move towards hard-to-express proteins. As well as many enzymes dedicated to the eradication of ROS, such as caspases, peroxidases and superoxide dismutases (SODs) the cell maintains a glutathione pool to buffer the increase of ROS (Lu, 2009). Design of Experiment models were designed and implemented using the growth, productivity and ROS content data from batch experiments in order to design anti-oxidant supplementation strategies. Two rounds of fed-batch screening were performed and a feeding strategy identified that improved the growth and ROS burden of three cell lines producing the same recombinant MAb product. A directed evolution strategy was employed to engineer oxidative stress resistant host cell lines through chronic exposure to Hydrogen Peroxide. Following transfection with a recombinant MAb product, the novel engineered cell line consistently outperformed the original cell line in terms of growth and ROS content, in both transient and stable transfection processes. Doubling time of stably transfected evolved cell line was reduced to 23 hours, a substantial time frame reduction. A link between ROS level reduction and improvement in cell line performance was demonstrated, with further investigation needed to unpick the mechanistic underpinnings of the oxidative stress resistance as well as to attempt to address the imbalance of improvements in growth compared to productivity.
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Castro, Giner Francesc. "Genetic and environmental factors in asthma: a population based European study." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7194.
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L'asma és una malaltia d'etiologia complexa, formada per factors genètics i ambientals, on la interrelació de ambdós factors mitjançant interaccions gen-ambient juga un paper clau. L'objectiu d'aquesta tesi ha sigut aprofundir en el coneixement del paper dels polimorfismes genètics, i la seva interacció amb factors ambientals, en la ocurrència d'asma, atòpia i hiperreactivitat bronquial. Aquest objectiu ha estat desenvolupat a través de la replicació de variants genètiques prèviament identificades, l'avaluació d'interaccions gen-ambient i la identificació de nous gens de susceptibilitat mitjançant un disseny basat en el genotipatge de variants genètiques all llarg del genoma en pools d'ADN. La tesi ha estat majoritàriament duta a terme dins l'estudi European Community Respiratory Health Survey (ECRHS) que està comprès per 5.000 individus seguits durant 9 anys, pels quals es disposa d'un qüestionari complet sobre símptomes respiratoris, avaluacions clíniques, informació sobre exposicions ambientals i mostres de ADN. Aquesta tesi a replicat l'associació del polimorfismes dels gens TNFA i NPSR1 amb asma. A més s'han establert les interaccions entre TNFA i obesitat, NQO1 i contaminació atmosfèrica, i NPSR1 i edat d'inici d'asma. L'anàlisi de pools d' ADN ha permès associar la regió on es situa el gen SGK493 amb atòpia. Aquesta tesi contribueix al coneixement de l'etiologia d'asma amb la identificació i replicació d'associacions genètiques i interaccions gen-ambient.Asthma is a disease with a complex etiology, involving multiple genetic and environmental factors, and with an important role of the interplay of these factors through gene-environment interactions. In this thesis I aimed to advance our knowledge on the importance of genetic polymorphisms and their interaction with environmental data for the occurrence of asthma and related phenotypes (atopy and bronchial hyperreactivity). This objective was developed through the replication of genetic associations previously reported, the assessment of gene-environment interactions and the identification of new susceptibility genes using genome-wide analysis based on a pooling DNA strategy. The thesis was, mostly, performed within the European Community Respiratory Health Survey (ECRHS). This cohort has information and DNA samples from approximately 5,000 adult subjects followed-up for 9 years, with extensive questionnaires on respiratory symptoms, clinical evaluations and information on environmental exposures. This thesis replicates previous effects on asthma of polymorphisms in TNFA and NPSR1 genes. In addition, interactions have been established between TNFA and obesity, NQO1 and air-pollution, and NPSR1 and age at onset of asthma. The approach based on genome-wide analysis of DNA pools identified the SGK493 region being associated with atopy. This thesis contributes to the understanding of the etiology of asthma through the identification and replication of genetic associations and gene-environment interactions.
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Alkazemi, Dalal Usamah. "Oxidative stress as a cardiovascular risk factor in Canadian Inuit." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114158.
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A decline in the traditional food consumption among the Inuit poses a nutritional problem, as it provides nutrients associated with protection from cardiovascular diseases (CVD). Controversy exists, however, regarding oxidative stress status among Inuit due to possible higher tissue oxidizability of n-3 polyunsaturated fatty acids (PUFA) from the traditional Inuit n-3 PUFA rich diet and their dietary exposure to pro-oxidative contaminants such as methylmercury and polychlorinated biphenyls (PCBs). We proposed that determining whole body oxidative stress status via the gold standard isoprostane biomarker that reflects an overall response to the various metabolic and xenobiotic burdens could be an indicator of the adaptations and predispositions of the Inuit to CVD. The objectives of this thesis were: (i) to quantify plasma levels of F2-isoprostanes, F3-isoprostanes, and isofurans and to assess their relationship to cardiometablic risk factors; (ii) to evaluate the relationship between the selenium (Se) status and plasma isoprostanes and to assess the interrelationship between dietary methylmercury exposure and tissue selenium on oxidative stress status; (iii) to examine the impact of decreased consumption of traditional foods on oxidative stress parameters; and (iv) to evaluate the pro-oxidant contribution of PCBs on oxidative stress status. A series of cross-sectional studies were conducted using data from the International Polar Year Inuit Health Survey (2007-2008). Cross-sectional analyses were conducted to examine the relationship between diet (Se, n-3 and n-6 PUFAs, trans and saturated fat), contaminants (MeHg and PCBs), obesity, and cardiovascular risk factors including hypertension, dyslipidemia, smoking and C-reactive protein in relation to oxidative stress using the gold standard F2-isoprostanes and the novel isoprostane biomarkers F3-isoprostanes and isofurans. Plasma levels of isoprostanes were determined by gas chromatography/negative ion chemical ionization/mass spectrometry methodology. Multivariate analyses were employed to determine final correlates of isoprostanes. Results showed that the Inuit are protected from mercury-induced oxidative stress because of their high Se status and that highest consumers of traditional foods were most protected. The isoprostane isoforms, F2-isoprostanes and isofurans, were both associated with increased obesity. F2-isoprostanes and isofurans were additionally associated to C-reactive protein and blood pressure. The F3-isoprostane isoform was shown to be quantifiable for the first time in human plasma, which was likely due to the C20:5n-3 rich Inuit diet. F3-isoprostanes and isofurans were more related to contaminants than F2-isoprostanes. Generally, this thesis demonstrates that the contaminants in the Arctic do not appear to pose a significant oxidative stress risk among the Inuit; however, shifting away from the traditional food is associated with obesity and inflammatory-induced oxidative stress. An important finding is that each isoprostane isoform has a unique attribute to explain the potential CVD risk and that simultaneous measurement of isoprostane species provides an advantageous mechanistic insight into oxidative stress status not captured by F2-isoprostanes alone.Une baisse dans la consommation des aliments traditionnels chez les Inuits pose un problème nutritionnel car elle fournit des nutriments associés à la protection contre les maladies cardio-vasculaires (MCV). Il existe une controverse, cependant, en ce qui concerne le stress oxydatif chez les Inuits en raison de l'oxydabilité des tissus plus élevée possible de n-3, des acides gras polyinsaturés (AGPI) de l'alimentation traditionnelle des Inuits rich en AGPI n-3, et leur exposition alimentaire à des pro-oxydants et des contaminants tels que le méthylmercure et les biphényles polychlorés (BPC). Nous avons proposé que la détermination de tout état de stress oxydatif du corps via la méthode de l'étalon-or isoprostanes, qui reflètent une réponse globale aux différentes charges métaboliques et des xénobiotiques, puisse être un indicateur des adaptations et des prédispositions des Inuits aux maladies cardiovasculaires. Les objectifs de cette thèse sont les suivants: (i) de quantifier les concentrations plasmatiques de F2-isoprostanes, F3-isoprostanes, et isofurans et d'évaluer leur relation avec les facteurs de risque cardiometabolique (ii) d'évaluer le lieu entre le statut en sélénium et les isoprostanes plasmatiques et d'évaluer la relation entre l'exposition au méthylmercure et du sélénium alimentaire tissus sur un état de stress oxydatif, (iii) d'examiner l'impact de la diminution de la consommation d'aliments traditionnels sur les paramètres du stress oxydatif, et (iv) d'évaluer la contribution des PCB sur le proxidant d'un état de stress oxydatif. Une série d'études transversales ont été réalisées en utilisant les données de l'Enquête sur l'Année Polaire Internationale de la Santé des Inuits (2007-2008). Les analyses transversales ont été menées pour étudier la relation entre l'alimentation (sélénium (Se), n-3 et n-6 AF, gras trans et saturés), les contaminants (MeHg et les PCB), l'obésité et les facteurs de risques cardiovasculaires comme l'hypertension, la dyslipidémie, le tabagisme et la protéine C réactive par rapport à un stress oxydatif avec l'étalon-or F2-isoprostanes et les nouveaux biomarqueurs isoprostane F3-isoprostanes et isofurans. Les concentrations plasmatiques des isoprostanes ont été déterminées par chromatographie en phase gazeuse, par l'ionisation négative chimique d'ions et par la méthode de spectrométrie de masse. Des analyses variées ont été utilisées pour déterminer les corrélats finals de isoprostanes. Les résultats ont montré que les Inuits sont protégés par le mercure causé par le stress oxydatif en raison de leur statut en sélénium élevée, et que les consommateurs d'aliments traditionnels ont été les plus protégés. Tous les isoformes isoprostanes ont été associés à l'obésité. Les F2-isoprostanes et isofurans ont en outre été associés à la protéine C réactive et de la pression artérielle. Aussi, les F3-isoprostanes et isofurans sont davantage liés aux contaminants que les F2-isoprostanes. En règle générale, cette thèse montre que les contaminants dans l'Arctique ne présentent aucun risque sur le stress oxydatif, mais que l'abandon aujourd'hui de la nourriture traditionnelle est associé à l'obésité et le stress induit par l'oxydation inflammatoire. Une constatation importante est que chaque isoprostane possède un attribut unique qui explique le risque potentiel de maladies cardio-vaculaires, et une mesure simultanée des isoprostanes donne un aperçu mécanistique avantageuse dans le stress oxydatif pas capturé par les F2-isoprostanes.
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Harris, Jessica Lynn. "INVESTIGATIONS INTO MODULATION OF BRAIN OXIDATIVE STRESS BY VARIOUS INTERVENTIONS." UKnowledge, 2012. http://uknowledge.uky.edu/chemistry_etds/12.
Full textAbstract:
In this thesis study we examined glycogen synthase kinase-3β (GSK-3β) and its effects over Nrf2 and Pin 1 as it relates to Alzheimer’s disease (AD). AD is a neurodegenerative disease characterized by a prolonged high oxidative environment. Transcription factor Nrf2 is vital in the brain’s defense against oxidative insults through its up-regulation of over 100 antioxidants. Depletion of the brain’s antioxidant defense system results in intolerance to an oxidative environment, contributing to the progression of AD. The regulatory Pin 1 protein promotes cellular homeostasis, and when down-regulated results in increased deposits of neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques, the two pathological hallmarks of AD.
Using aged SAMP8 mice treated with antisense oligonucleotide (AO) directed at GSK-3β and random AO, the data presented here demonstrate decreased oxidative stress and increased Nrf2 transcriptional activity and Pin 1 levels as a result of the down-regulation of GSK-3β. Collectively, these results implicate GSK-3β activity in the increased oxidative stress of AD and support its inhibition as a possible therapeutic treatment for the disease. Further, we elucidate a possible mechanism connecting GSK-3β to the loss of tolerance to an oxidative environment and increased deposits of NFTs and Aβ plaques observed in AD.
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Wang, Bo. "Transcriptional regulation of the human NAD(P)H: quinone oxidoreductase gene during oxidative stress." Thesis, University of East Anglia, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262435.
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Lourenço, Rogério Ferreira. "Caracterização dos sistemas ChrR-σR e CC3476σT na resposta de C. crescentus aos estresses oxidativo e osmótico." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-27112008-100001/.
Full textAbstract:
Caulobacter crescentus está entre as bactérias cujos genomas codificam um grande número de fatores sigma ECF, os quais estão envolvidos na regulação transcricional de conjuntos limitados de genes em resposta a uma variedade de estímulos ambientais. No presente trabalho, dois fatores sigma ECF de C. crescentus, σR e σT , foram caracterizados funcionalmente. Os dados mostraram que σR e σT e são mantidos em níveis reduzidos de expressão sob condições fisiológicas de crescimento da bactéria, devido à ação das proteínas ChrR e CC3476, respectivamente. Contudo, durante a exposição de C. crescentus ao cádmio, hidroperóxido orgânico, oxigênio singlete ou à radiação UVA, a expressão de σR é induzida de maneira dependente do próprio fator sigma. Análises de transcriptoma mostraram que σR regula a expressão de genes envolvidos na proteção celular contra danos oxidativos. Central para essa resposta transcricional mediada por σR é a inativação de ChrR, sendo os resíduos C186 e C188 desta proteína necessários para a percepção de cádmio, mas não de hidroperóxido orgânico ou oxigênio singlete. Em adição, os dados mostraram que sigR e dois outros genes dependentes de σR (cfaS e CC2258) são essenciais para a sobrevivência de C. crescentus quando os danos oxidativos são gerados nas células por longos períodos. Similarmente, a expressão de σT aumenta em nível transcricional nesta bactéria sob condições de hiperosmolaridade induzidas por NaCl ou sacarose. Além de se auto-regular positivamente, σT controla a expressão de σU e σE , constituindo uma cascata de expressão de fatores sigma ECF em C. crescentus. σT, mas não σU e σE , desempenha um papel essencial na sobrevivência dessa bactéria durante a exposição ao NaCl e sacarose. Adicionalmente, a ausência de σT resulta numa sensibilidade aumentada dessa bactéria ao H2O2, apesar de não ser observada indução da expressão dos genes sigT, sigU e sigE durante essa condição de estresse. Diante do exposto, o presente trabalho contribuiu para a compreensão de dois mecanismos de adaptação da bactéria C. crescentus aos estresses oxidativo ou osmóticoCaulobacter crescentus is among the bacteria whose genomes encode a high number of ECF sigma factors, which are involved in the transcriptional regulation of a limited set of genes in response to several environmental signals. In the present work, two ECF sigma factors from C. crescentus, σR e σT, were functionally characterized. Data showed that σR e σT are maintained in reduced expression levels under physiological growth conditions, due to the action of ChrR and CC3476, respectively. However, during C. crescentus exposure to cadmium, organic hydroperoxide, singlet oxygen and UVA irradiation, σR expression is positively auto-regulated. Transcriptome analyses showed that σR regulates the expression of genes involved in protecting cells against oxidative damages. Central to this transcriptional response is the inactivation of ChrR, with residues C186 and C188 of this protein being necessary for sensing cadmium but not organic hydroperoxide or singlet oxygen. In addition, data revealed that sigR and two other σR-dependent genes (cfaS and CC2258) are essential for C. crescentus survival when oxidative damages are generated in the cells for long periods of time. Similarly, σT expression increases at a transcriptional level in this bacterium under hyperosmotic conditions induced by NaCl or sucrose. Besides being positively auto-regulated, σT independently controls the expression of σU and σE, forming an expression cascade of ECF sigma factors in C. crescentus. σT, but not σU or σE, displays an essential role in C. crescentus survival during NaCl or sucrose exposure. Additionally, the absence of σT leads to an increased sensitivity of this bacterium to H2O2, despite the absence of induction in sigT, sigU or sigE expression under the same stress condition. Therefore, the present work has contributed to the understanding of two mechanisms of C. crescentus adaptation to oxidative and osmotic stresses