Dissertations / Theses: 'Isoprostany'

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Silva, Graziela Biude. "Estado nutricional relativo ao zinco de pacientes com artrite reumatoide e sua relação com o estresse oxidativo e o polimorfismo Arg213Gli no gene da superóxido dimutase 3." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-27022014-103035/.

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A artrite reumatoide (AR) é uma doença auto-imune de etiologia desconhecida caracterizada por uma inflamação poliarticular simétrica da membrana sinovial que acomete com maior frequência as articulações das mãos, punhos e pés. Estudos mostram que há um aumento do estresse oxidativo nestes pacientes e este fato pode ser atribuído à diminuição da ingestão de substâncias antioxidantes refletindo no aumento da produção de espécies reativas de oxigênio (ERO). Além disso, a presença de polimorfismos em enzimas antioxidantes como o Arg213Gli no gene da enzima superóxido dismutase 3 podem influenciar neste dano oxidativo. Portanto, o estudo teve como objetivo avaliar o estado nutricional relativo ao zinco de pacientes com artrite reumatoide e sua relação com o estresse oxidativo e o polimorfismo Arg213Gli no gene da SOD3. Foram selecionadas 59 mulheres diagnosticadas com AR (59,9±18,3 anos) atendidas no Setor de Reumatologia do Hospital São Paulo/Universidade Federal de São Paulo, que fizeram parte do grupo caso, e 56 mulheres saudáveis (35,5±9,9 anos) recrutadas no campus da Universidade de São Paulo, que fizeram parte do grupo controle. A coleta de sangue venoso foi destinada para avaliação das concentrações plasmática e eritrocitária de zinco, da atividade das enzimas glutationa peroxidase (GPx) e superóxido dismutase (SOD), e do polimorfismo Arg213Gli. A urina de 24 horas foi coletada para as análises de zinco, creatinina e 8-isoprostanos. A avaliação do consumo dietético de zinco foi feita por meio de três recordatórios alimentares de 24 horas. A análise estatística foi feita no software SPSS 14.0 por meio de testes de comparações de médias e correlações selecionados de acordo com a distribuição da normalidade e considerando p significativo menor que 5%. As concentrações plasmáticas de zinco foram significativamente menores para o grupo caso quando comparadas ao grupo controle (53,4±9,8 µg/dL e 58,2±10,1 µg/dL, respectivamente; p=0,011). Com relação às concentrações de zinco eritrocitário e urinário não houve diferença significativa entre os grupos (p=0,219 e p=0,695, respectivamente). O percentual de inadequação do consumo de zinco foi de 98,9% para o grupo caso e 58% para o grupo controle. A atividade da SOD foi significativamente menor no grupo caso (1333,8 ±420,8 U/gHb) do que no grupo controle (1755,0 ±525,5 U/gHb) (p<0,001), assim como a atividade da GPx (38,2 ±17,0 U/gHb e 52,6 ±14,4 U/gHB, respectivamente) (p<0,001). As concentrações de 8-isoprostanos não diferiram entre os grupos caso e controle, (133,8 ±175,4 ng/mmol de creatinina e 139,3 ± 52,7 ng/mmol de creatinina; p=0,836, respectivamente). Em relação à genotipagem do SNP Arg213Gli não foi encontrado nenhuma participante com o genótipo homozigoto (Gli/Gli) para o polimorfismo. No grupo caso, apenas uma participante apresentou o genótipo heterozigoto (Arg/Gli). Os resultados apresentados indicam que as pacientes com AR estão deficientes em zinco e apresentam um aumento do estresse oxidativo, sugerindo a necessidade de uma suplementação deste mineral.
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by a symmetrical polyarticular inflammation of synovial membrane that affects most often the joints of the hands, wrists and feet. Studies show that there is an increase of oxidative stress in these patients and this fact can be attributed to decreased intake of antioxidants reflecting in the increased production of reactive oxygen species (ROS). Furthermore, the presence of polymorphisms in antioxidant enzymes such as Arg213Gli in the superoxide dismutase gene may influence this oxidative damage. Thus, the study aimed to evaluate the nutritional status of zinc in patients with rheumatoid arthritis and its relation to oxidative stress and the polymorphism Arg213Gli in SOD3 gene. We selected 59 women diagnosed with RA ( 59.9 ± 18.3 years) which make clinical monitoring at the Hospital São Paulo/Federal University of São Paulo, who were part of the case group, and 56 healthy women ( 35.5 ± 9 , 9 years) recruited on the campus of the University of São Paulo, who were part of the control group. The venous blood collection was destined to evaluate plasma and erythrocyte zinc, activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the polymorphism Arg213Gli. The 24-hour urine was collected for the analyzes of zinc, creatinine and 8- isoprostane. The assessment of dietary intake of zinc was performed by three 24-hour dietary recall. Statistical analysis was performed with SPSS 14.0 by testing of mean comparisons and correlations selected according to the distribution of normality and considering significant p less than 5 %. The plasma zinc concentrations were significantly lower in the case group compared to the control group (53.4 ± 9.8 µg/dL and 58.2 ± 10.1µg/dL, respectively, p= 0.011). In relation to the concentrations of erythrocyte and urinary zinc, no significant difference was observed between groups (p= 0.219 and p=0.695, respectively). The percentage of inadequate zinc intake was 98.9% for the case group and 58% for the control group . The SOD activity was significantly lower in the case group (1333.8 ± 420.8 U/gHb) than in the control group (1755.0 ± 525.5 U/gHb) (p < 0.001), as well as the activity of GPx (38.2 ± 17.0 U/gHb and 52.6 ± 14.4 U/gHb, respectively) (p< 0.001). The 8-isoprostane concentrations did not differ between case and control groups (133.8 ± 175.4 ng/mmol creatinine and 139.3 ± 52.7 ng/mmol creatinine, p= 0.836, respectively). Regarding Arg213Gli SNP genotyping was not found any participant with the homozygous genotype (Gly/Gly) for the polymorphism. In case group, only one participant had the heterozygous genotype (Arg/Gly). The presented results indicate that RA patients are deficient in zinc and have an increased oxidative stress, suggesting the need for a supplementation of this mineral.

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Čumová, Martina. "Využití hmotnostní spektrometrie ke stanovení markerů oxidativního stresu a mykotoxinů." Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2015. http://www.nusl.cz/ntk/nusl-233402.

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The first topic presented in the dissertation thesis is determination of isoprostanes as markers of oxidative stress and other compounds affected by presence of oxidative stress. Isoprostanes iPF2-III, iPF2-VI, iPF2-VI, astaxanthin and polyunsaturated fatty acids (PUFA), especially arachidonic acid (AA) were monitored in Atlantic salmon eggs (Salmo salar). Methods for the determination of these compounds have been developed and optimized using chromatographic separation coupled to conventional or mass spectrometric detection. Freshly laid eggs, eyed embryos and non-viable eggs were used to test a general hypothesis that egg viability can be affected by susceptibility to oxidative stress, either through the specific fatty acid concentration and/or the antioxidant capacity of the eggs. Levels of isoprostanes and arachidonic acid (AA) were significantly higher in non-viable eggs than in control (eyed embryos) as well as relative abundance of PUFA. While no difference of isoprostanes was found between freshly laid and control those from the Atlantic stock except iPF2-VI which was observed under the LOQ in the control. Higher levels of PUFA and AA in comparison with the control were observed in the freshly laid eggs. However, the only statistically significant difference was observed in the amount of astaxanthin. Different levels of PUFA and astaxanthin may be related to their biochemical consumption during the development of eggs. This work evaluated potential effect on the viability of eggs Salmo salar due to the presence of oxidative stress. The monitoring of mycotoxins in food and feed was the subject of the second topic. Mycotoxins are secondary metabolites produced by fungi. They are ubiquitous undesirable natural contaminants that are toxic for humans and animals. Today are known more than 500 mycotoxins. However, only few of them are regulated by the European Union. The European Food Safety Authority (EFSA) was asked by the European Commission to provide a scientific opinion on other mycotoxins for which statutory limits could be developed. In this study is proposed simultaneous screening allowing fast, reliable and sensitive approach, identification and quantification of 17 mycotoxins in food and feed sample. The method includes both mycotoxins regulated by the EU and selected mycotoxins required by the EFSA (aflatoxins, deoxynivalenol, nivalenol, zearalenone, fumonisin, ochratoxin A, T-2 toxin, HT-2 toxin, enniatins and beauvericin). Analytes are isolated by the modified QuEChERS method. For separation and target mycotoxins detection, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC –MS/MS) was employed. The method also allows determination of ergot alkaloids (ergocornine, ergosine, ergocryptine, ergocristine and their respective epimers). The developed method was used either for monitoring mycotoxins and ergot alkaloids in feed and raw materials and barley and malt prepared from it.

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Martinez, Bermudez Ana Katherine. "Isoprostanes in brain endothelial cell death." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21605.

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Oxygen free radicals have been implicated in several diseases including ischemic stroke, and myocardial infarction. They can trigger chain reactions like peroxidation of membrane phospholipids, leading to osmotic imbalance and cell death. Isoprostanes are stable products of lipid peroxidation that have a constrictor effect on the vasculature and bronchii. As isoprostanes are abundantly generated in tissues under oxidant stress, we have hypothesized that they could be related to endothelial dysfunction observed during ischemia/reperfasion by affecting endothelial cell survival. The effects of 8-iso-PGE2 and 8-iso-PGF2alpha, two abundantly produced isoprostanes, were studied on porcine endothelial cultures and isolated brain microvessels. Cell survival was evaluated by MTT reduction, double staining with DNA-binding fluorochromes and in situ DNA fragmentation labeling,
8-Iso-PGF2alpha (1--10 nM) induced 20--25% cell death in endothelial cultures after 24 h coincident with similar increase in the number of cells that become permeable to PI. On the contrary, 8-iso-PGE 2 did not affect endothelial cell survival. Approximately 9% of the cells suffered apoptosis. This percentage remained unchanged regardless the treatment. Several observations indicate a role for thromboxane A2 to mediate 8-iso-PGF2alpha-induced death: (1) the levels of thromboxane A2 increased dramatically in endothelial cultures after 8-iso-PGF2alpha-treatment; (2) inhibitors of thromboxane synthase, CGS12970 and U6355A and Ibuprofen, a non-selective inhibitor of cyclooxygenases, reverted the effect of the isoprostane; (3) analogs of thromboxane A2 U46619 and IBOP, reproduce the effect of 8-iso-PGF 2alpha after 24 h. 8-Iso-PGF2alpha also decreased endothelial viability on isolated brain microvessels. These results suggest, that 8-iso-PGF2alpha, might be a direct contributor to ischemia/reperfusion injury.

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Martinez, Bermudez Ana Katherine. "Isoprostanes in brain endothelial cell death." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0025/MQ50832.pdf.

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Henry, Olivier. "Synthèses totales de métabolites de la 15-F2t-Isoprostane." Montpellier 2, 2002. http://www.theses.fr/2002MON20009.

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Freitas, Betânia de Jesus e. Silva de Almendra 1962. "Possíveis marcadores de estresse oxidativo para câncer de pele não melanoma : efeito da suplementação de vitamina C, E e mineral zinco em indivíduos que tiveram câncer de pele não melanoma." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312979.

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Orientador: Patrícia Moriel
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-26T00:37:20Z (GMT). No. of bitstreams: 1 Freitas_BetaniadeJesuseSilvadeAlmendra_D.pdf: 2657931 bytes, checksum: d4646bbc60ccc13e11ca7d806b4f75dc (MD5) Previous issue date: 2014
Resumo: Estudos acerca da influência do estresse oxidativo sobre o equilíbrio cutâneo, sobretudo por seus efeitos devastadores sobre a integridade da pele, são essenciais para a proposição de estratégias de intervenção preventivas para o desenvolvimento do câncer de pele. O objetivo do estudo foi comparar o estresse oxidativo de indivíduos que tiveram e não tiveram câncer de pele não melanoma e avaliar o efeito da suplementação combinada de vitaminas C, E e mineral Zinco no estresse oxidativo de indivíduos que apresentaram a doença. O estudo foi dividido em duas fases: a fase 1 foi um estudo transversal com controles, cuja população foi constituída por pessoas saudáveis (n = 24) e o grupo caso constituído por indivíduos que apresentaram câncer de pele não melanoma já submetidas a tratamento cirúrgico (n = 60). E a fase 2, um ensaio clínico randomizado e duplo cego, no qual os pacientes do grupo caso foram randomizados em dois subgrupos: grupo placebo (n = 34) e grupo suplementado (n = 26) com 50 mg de vitamina C, 60 mg de vitamina E e 40 mg de Zinco durante 8 semanas. As amostras de sangue dos sujeitos foram obtidas no período basal e após intervenção para a avaliação dos biomarcadores de estresse oxidativo (F2-isoprostano, nitrito, substâncias reativas ao ácido tiobarbitúrico (TBARS) e capacidade antioxidante total). O consumo alimentar habitual e o estado nutricional dos sujeitos foram avaliados. Para identificação dos fatores associados ao câncer de pele foi utilizada a análise de regressão logística univariada e multivariada. O nível de significância adotado para este estudo foi de 5%. A maioria dos pacientes estudados foram do sexo feminino com idade superior a 50 anos. Os pacientes do grupo caso apresentaram mais elevadas concentrações séricas dos biomarcadores de estresse oxidativo, sendo que as concentrações de F2-isoprostano estavam significativamente mais elevadas em comparação com os controles. Após suplementação não houve diferença estatística entre os grupos placebo e suplementado em relação aos marcadores de estresse oxidativo. A idade e o F2-isoprostano podem ser marcadores de risco para o câncer de pele não melanoma, a cada ano a mais para o fator idade aumenta em 12% a chance de câncer e cada unidade a mais na medida do marcador aumenta em 4% a chance de câncer. Os resultados mostraram prevalência de sobrepeso no grupo controle com diferença estatística significativa em relação ao grupo caso. As concentrações dietéticas dos minerais antioxidantes zinco, cobre e selênio do grupo caso foram estatisticamente inferiores em relação aos controles e não houve diferença estatística nas concentrações dietéticas dos nutrientes antioxidantes entre os grupos suplementado e placebo. Este estudo sugere que pessoas diagnosticadas com câncer de pele não melanoma e que no momento da realização da pesquisa não mais apresentavam a doença, mostravam elevado estresse oxidativo, quando comparadas a pessoas saudáveis. A suplementação de antioxidantes pelo período de tempo realizado no trabalho não provocou redução significativa nas concentrações dos marcadores de estresse oxidativo dos pacientes. O estudo ainda sugere que o marcador de estresse oxidativo F2-isoprostano pode ser utilizado como um fator de risco para o desenvolvimento do câncer de pele não melanoma
Abstract: Studies investigating the influence of oxidative stress on skin homeostasis, especially for its devastating effects on skin integrity, are essential for the development of preventive intervention strategies for skin cancer. The goal of this study was to compare the concentrations of oxidative stress biomarkers in blood between individuals with and without non-melanoma skin cancer and evaluate the effect of combined supplementation with vitamins C, E, and the mineral zinc on oxidative stress in skin-cancer patients. The study was divided into two stages: stage 1 was cross-sectional study with controls, whose population consisted of healthy individuals (n = 24) and the case group included individuals who had non-melanoma skin cancer undergoing surgery (n = 60). And the second phase a randomized, double blind clinical trial where patients in the case group were randomized into two subgroups: placebo (n =34) and a supplemented group (n = 26) who received 50 mg of vitamin C, 60 mg of vitamin E, and 40 mg of zinc for 8 wk. Blood samples were taken from the subjects before and after intervention to evaluate levels of oxidative stress biomarkers (F2-isoprostane, nitrite, thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity. The usual food consumption and nutritional state of the subjects were also evaluated. Multivariate and univariate logistics regression analysis were used to identify factors associated with the development of skin cancer. The level of significance adopted for this study was 5%. The majority of participants were women over the age of 50. The patients in the case group had higher serum concentrations of oxidative stress biomarkers, and the levels of F2-isoprostane were significantly higher than the controls. After antioxidant supplementation there was no statistical difference in the markers of oxidative stress among the placebo and supplemented groups. Age and F2-isoprostane may be effective biomarkers for estimating the risk of non-melanoma skin cancer development. Moreover, the risk of cancer increases with age at a rate of 12% per year, while an increase in concentration of these biomarker in blood increases the risk of cancer by 4%. These results showed a prevalence of excess weight in the control group with significant statistical difference from the case group. The dietary intake of the mineral antioxidants zinc, copper, and selenium of the case group were significantly lower than the control group, and there was no statistical difference in the dietary intake of the antioxidant nutrients among the supplemented and placebo groups. This study suggests that people diagnosed with non-melanoma skin cancer and those in remission at the time of the study, exhibited higher concentration oxidative stress than healthy individuals. The antioxidant supplementation by period the work performed did not cause significant reduction in serum concentrations of oxidative stress biomarkers of the patients. The results suggest that the concentration of the oxidative stress biomarker, F2-isoprostane, may serve as risk factor for non-melanoma skin cancer development
Doutorado
Ciencias Biomedicas
Doutora em Ciências Médicas

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Pinot, Edith. "Synthèse totale des quatre diastéréoisomères de la 15-E2t-isoprostane." Montpellier 2, 2008. http://www.theses.fr/2008MON20014.

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Dinca, Emanuela [Verfasser], and Thomas [Akademischer Betreuer] Lindel. "Oxidative Reactions of Enolates and Their Application to Total Syntheses of 15-F2t-Isoprostane and Potential Secondary Metabolites of 15-E2-Isoprostane / Emanuela Dinca ; Betreuer: Thomas Lindel." Braunschweig : Technische Universität Braunschweig, 2013. http://d-nb.info/1175821438/34.

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Greaves, Kim. "Influence of Isoprostane F2[subscript a] -III on reflow after myocardial infarction." Thesis, King's College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439447.

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Clarke, Deborah Lee. "The role of prostanoids and isoprostanes in airway inflammation." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406342.

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Noschka, Erik. "Can isoprostanes be used to predict survival in horses with colic?" Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/44193.

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Approximately 4% of horses suffer from one colic episode per year. The outcome is fatal in 11% of cases. F2-isoprostanes are the "gold standard" for assessment of oxidative stress in vivo and have been used extensively to quantify lipid peroxidation in association with risk factors in various diseases in humans. Because horses with colic may have intestinal ischemia and/or inflammation characterized by oxidative stress and increased production of isoprostanes, measurement of isoprostane concentrations in colicky horses may be of clinical value. The purpose of this study was to gather preliminary data on the feasibility of using urine isoprostane concentrations as an early screening tool for the severity of colic and to determine the need for surgery. The long term goal of this investigation is to reduce the number of deaths due to colic by developing a stall-side test capable of identifying horses needing surgery as early as possible and expediting their timely referral. We hypothesized that urine isoprostanes and isoprostane metabolites would be significantly higher in horses with colic compared to normal horses and that they can be used an indicator for the need for surgical intervention. Urine samples were collected from 42 normal horses and 38 horses with colic (21 medical and 22 surgical). Urine isoprostane and isoprostane metabolite concentrations were measured by mass spectrometry and normalized by urine creatinine (Cr) concentrations. Statistical analysis was performed using a one way ANOVA (Tukeyâ s post-hoc comparison) and a 2 sample t-test. Significance was set at P<0.05. Mean (Â± SD) concentrations of isoprostanes and isoprostane metabolites were significantly higher in urine samples of horses with colic (2.94 Â± 1.69 ng/mg Cr and 0.31 Â± 0.22 ng/mg Cr, respectively) compared to healthy horses (1.89 Â± 1.39 ng/mg Cr and 0.22 Â± 0.08 ng/mg Cr, respectively). Urine isoprostane metabolite concentrations were significantly higher in horses undergoing surgery (0.38 Â± 0.28 ng/mg Cr) compared to healthy control horses and medically treated colic horses (0.26 Â± 0.11 ng/mg Cr). Non-survivors had significantly higher mean urine isoprostane metabolite concentrations (0.47 Â± 0.39 ng/mg Cr) compared to healthy control horses and surviving colic horses (0.29 Â± 0.24 ng/mg Cr). Since urinary concentrations of isoprostane metabolites are increased in horses suffering from colic and in non-survivor colic horses, the measurement of urine concentrations of isoprostane metabolites may be an important prognostic indicator in equine colic.
Master of Science

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Gopaul, Nitin Kumar. "Analysis of Fâ†2-isoprostanes as markers of lipid peroxidation." Thesis, Oxford Brookes University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363749.

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Colombini, Marjorie Paris. "Exposição aguda ao material particulado total em suspensão proveniente de diferentes fontes e suas repercussões nas respostas inflamatórias, sistêmica e local, em ratos." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-11122007-153039/.

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Introdução: Poluição do ar está associada ao aumento da morbidade e mortalidade e essas associações persistem mesmo a baixas concentrações do poluente e a exposições agudas. Objetivos: Avaliar a associação entre componentes de três diferentes fontes do Particulado Total em Suspensão (PTS) e resposta aguda inflamatória, local e sistêmica, em ratos saudáveis. Métodos: PTS proveniente de fonte automativa, industrial e da queima da cana de açúcar foram coletados em filtros de fibra de vidro, extraídos em água destilada por ultrassonificação, e instilados na traquéia de 45 ratos (15 em cada grupo). Vinte microgramas por mililitro dos PTS foram administrados em cada animal. A mesma quantidade de partículas de grafite em água destilada foi utilizada como controle. Marcadores inflamatórios de resposta local e sistêmica foram mensurados 24 horas após a exposição. Resultados: PTS proveniente da fonte automotiva apresentou altas concentrações de enxofre, ferro, chumbo e cobre e produziram efeito adverso local e sistêmico, evidenciado pelo aumento do óxido nítrico exalado (6,22 ppm ± 3,8), do número de plaquetas (743,7 x 103/mm3 ± 73,4), e dos níveis do fibrinogênio (312,1 ± 42,7 mg/dL) e fator VIII (185,1 ± 37,2%), maiores dos que os observados no grupo controle (p < 0,05). O PTS proveniente da queima da cana de açúcar, com altas concentrações de ferro e cobre, e moderadas de enxofre produziram maior estresse oxidativo pulmonar e cardíaco em comparação ao grupo-controle e fonte automotiva (p < 0,05). O PTS gerado a partir da fonte industrial, com significativa concentração de ferro e cobre, e alta quantia de cálcio mostrou maior resposta oxidativa pulmonar e cardíaca em comparação ao grupo-controle, embora com discreta resposta inflamatória sistêmica (p > 0,05). Conclusão: Os resultados mostram que em doses baixas e agudamente, a exposição ao material particulado total em suspensão induz respostas inflamatórias locais e sistêmicas e pode alterar os componentes da hemostasia. Estas respostas foram influenciadas e moduladas pela composição elementar dos materiais analisados. Além disso, estes resultados subsidiam os achados epidemiológicos que associam exposição ao material particulado com morbidade e mortalidade cardiovasculares.
Background: Air pollution is associated with both increased morbidity and mortality. These associations persist even at lower concentrations and shortterm exposure. Objectives: To assess the impact of the components of three different sources of Total Suspended Particles (TSP) on local and systemic inflammatory responses in healthy rats. Methods: TSP from automotive, industrial and biomass burning sources were collected in specific glass-fiber filters, extracted in distilled water by ultrasound and instilled into the trachea of 45 rats (15 in each group). Twenty micrograms for mililiter of TSP were administered to each animal. The same amount of graphite particles (carbon black) in distilled water was used as control. Inflammatory markers of local and systemic responses were measured 24 hours after the exposure. Results: Automotive-generated TSP presented high percentages of sulfur, iron and copper, producing local and systemic adverse effects evidenced by increases in exhaled nitric oxide (6.22 ppm ± 3.8), platelets (743.7 x 103/mm3 ± 73.4), fibrinogen (312.1 ± 42.7 mg/dL) and factor VIII (185.1 ± 37.2 %) levels, which proved higher than those observed in the black carbon group (p < 0,05). Biomass burning TSP with high percentage of iron and copper and moderate levels of sulfur produced the greatest pulmonary and cardiac oxidative stresses compared to the black carbon and automotive groups (p < 0,05). Industry-generated TSP with relevant amounts of iron, copper, and high percentages of calcium showed higher pulmonary and cardiac oxidative responses than those observed for the control group, along with a slightly systemic response (p > 0,05). Conclusion: The results showed that the acute exposure to the total suspended particles at low concentrations induces local and systemic inflammatory responses and can change the hemostasis components. These effects were influenced and modulated by the elementary composition of the analyzed materials. Moreover, these results subsidize the epidemiologycal findings that associate exposure to the particulate matter with cardiovascular morbidity and mortality.

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Kromer, Brendan Michael. "The pathophysiology of the Fâ†2-isoprostanes with the coronary circulation." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287546.

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Hughes, C. M. "Oxidative stress, isoprostanes and micronutrient levels in patients with heart failure." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446122.

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Brault, Sonia. "Isoprostanes and lysophosphatidic acid : major lipid peroxidation products potentially involved in periventricular leukomalacia." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102480.

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Periventricular leukomalacia (PVL) is the principal form of brain injury in preterm neonates. In addition to the vasculopathy associated with hypoxicischemic injury, PVL is characterized by the loss of progenitor oligodendrocytes (OLs). Oxidant stress and lipid peroxidation increase in hypoxic-ischemic injuries, particularly in the immature brain. We hypothesized that the major lipid peroxidation products isoprostanes 15-F2t-IsoP and 15-E2t-IsoP, and lysophosphatidic acid (LPA) could be implicated in the pathogenesis of PVL by affecting the survival of brain OLs and microvascular endothelial cells (ECs).
Cytotoxicity of the lipid peroxidation products was assessed on cultured rat progenitor and mature OLs and piglet cerebromicrovascular ECs using the MTT assay. The two isoprostanes displayed different cytotoxic profiles. 15-E 2t-IsoP induced progenitor OL death but did not affect mature OL or microvascular EC survival. In contrast, 15-F2t-IsoP induced death of ECs but not of progenitor and mature OLs. As well, LPA triggered brain microvascular EC death. In all cases, cells did not exhibit classical features of apoptosis (nuclear condensation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL), caspases activation) but displayed signs of oncotic necrosis (propidium iodide incorporation, cell swelling, lactate dehydrogenase release). Cytotoxicity conveyed by both isoprostanes involved TxA2 synthesis, as determined by radioimmunoassay and by the protective effect of TxA2 synthase inhibitors. In addition, progenitor OLs were susceptible to 15-E2t-IsoP due to their low antioxidant defenses. On the other hand, LPA caused EC death through the LPA1 receptor which activated the stress activated protein kinases p38 MAPK and JNK; these kinases were responsible for the decreased intracellular glutathione content observed and the induction of iNOS which caused protein nitrosylation. EC death and neuromicrovascular degeneration caused by 15-F2t-IsoP and LPA were observed ex vivo on isolated microvessels and brain explants and in vivo, with intracerebroventricular infusion and intraocular injections.
These novel data implicate 15-E2t-IsoP, 15-F2t-IsoP and LPA as major lipid peroxidation products that may contribute to the genesis of PVL by affecting the survival of progenitor OLs and microvascular ECs.

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17

Laget, Jonas. "Biocommunication entre le tissu adipeux viscéral et la cellule bêta-pancréatique : isoprostanes et microARNs." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT010/document.

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Le diabète de type 2 résulte d’un déséquilibre entre les capacités de sécrétion de l’insuline par les cellules bêta-pancréatiques et son action au niveau de ses tissus cibles. Dans le prédiabète, l’hypersécrétion d’insuline compense l’insulino-résistance et cet état est généralement associé à l’obésité et à l’accumulation de tissu adipeux.L’objectif de ma thèse a été d’étudier la biocommunication entre le tissu adipeux viscéral et la cellule bêta-pancréatique lors du prédiabète et du diabète de type 2, en me focalisant sur deux médiateurs originaux, les isoprostanes et les miARNs. Nous avons observé une diminution de la sécrétion d’isoprostanes par le tissu adipeux péripancréatique au cours de l’obésité chez le rat Zucker fa/fa. Spécifiquement observé dans ce tissu adipeux ectopique, ce résultat s’explique par une induction des principales enzymes antioxydantes et une réduction de l’expression de la sPLA2 IIA chez les animaux obèses. Remarquablement, une des isoprostanes, la 15-F2t-Isoprostane ainsi que son épimère aux concentrations de 10 nM et 10 μM inhibent la sécrétion d’insuline gluco-stimulée dans les îlots pancréatiques isolés de rat Wistar. Cet effet pourrait s’expliquer par la liaison de cette isoprostane avec le récepteur au thromboxane A2, dont l’expression génétique et protéique a été mise en évidence pour la première fois dans les îlots de Langerhans et les cellules bêta. La réduction de l’inhibition de la sécrétion d’insuline chez le rat Zucker fa/fa, par une biocommunication paracrine, pourrait favoriser les mécanismes de compensation bêta-cellulaire. Par ailleurs, la production de miARNs, contenus dans des vésicules extracellulaires, par le tissu adipeux omental a été analysée chez l’homme par small RNAseq. Chez des patients obèses, la production de miARNs est modifiée lors de l’insulino-résistance et du diabète de type 2 avec des conséquences possibles sur la fonctionnalité des cellules bêta. Des miARNs différentiellement exprimés lors du diabète de type 2 pourraient ainsi participer à son apparition et représenter de nouveaux biomarqueurs et cibles thérapeutiques. Pour conclure, ces travaux de thèse ont permis de mettre en évidence de nouveaux mécanismes de biocommunication entre le tissu adipeux et les cellules bêta-pancréatiques
Type 2 diabetes occurs as a result of an unability of pancreatic beta-cells to meet the insulin demand in its target tissues. During prediabetes insulin hypersecretion compensate for insulin resistance and this state is usually associated with obesity and excess body fat.The aim of my thesis was to study the biocommunication between visceral adipose tissue and pancreatic beta-cells during prediabetes and type 2 diabetes, with a focus on two original mediators, isoprostanes and miRNAs. We observed a decrease in isoprostane secretion by peripancreatic adipose tissue during obesity in Zucker fa/fa rats. In this ectopic adipose tissue, this observation may be related to an induction of some antioxidant enzymes and a reduction of the expression of sPLA2 IIA in obese animals. Remarkably, 15-F2t-Isoprostane as well as its epimer used at concentrations of 10 nM and 10 μM inhibited glucose-stimulated insulin secretion in isolated pancreatic islets. This effect could be explained by the binding of isoprostanes to the thromboxane A2 receptor, whose gene and protein expression has been demonstrated for the first time in islets and beta-cells. In Zucker fa/fa rats, less inhibition of insulin secretion through a paracrine biocommunication, could favor beta-cell compensatory mechanisms. Furthermore, the production of miRNAs, contained in extracellular vesicles released by omental adipose tissue, was analyzed in humans by small RNAseq. In obese patients, miRNAs production is altered during insulin resistance and type 2 diabetes with possible consequences for beta-cell function. Differentially expressed miRNAs in type 2 diabetes may participate in its development and represent novel biomarkers and therapeutic targets. In conclusion, this thesis highlighted new biocommunication mechanisms between adipose tissue and beta-pancreatic cells

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18

Brien, Mélanie. "Étude des acides gras polyinsaturés et des F₂-isoprostanes dans le placenta en prééclampsie." Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27680.

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La prééclampsie est caractérisée par une hypertension gestationnelle accompagnée d’une protéinurie détectable après 20 semaines de grossesse. Une invasion anormale de l’endomètre par le placenta est à l’origine de la pathophysiologie. L’apparition d’une condition hypoxique placentaire est associée à un stress oxydatif ainsi qu’à un dérèglement de la synthèse et du transport des acides gras polyinsaturés vers le fœtus. L’oxydation non enzymatique de l’acide arachidonique, un acide gras insaturé oméga-6, mène à la formation potentielle de soixante-quatre isomères de F₂-isoprostanes. Ces derniers sont d’excellents biomarqueurs du stress oxydatif et peuvent jouer un rôle de vasoconstricteurs, lorsque libérés des phospholipides des membranes cellulaires par les phospholipases A₂. J’ai étudié les niveaux d’acides gras intacts et oxydés libérés par les phospholipases A₂ ainsi que la voie du thromboxane A₂ dans le placenta de grossesses normotensives et prééclamptiques. Mes travaux ont mis en lumière que le plasmalogène, une classe particulière de phospholipides riche en acides gras polyinsaturés, est augmenté dans le placenta en prééclampsie. De plus, les F₂-isoprostanes libres se retrouvent en plus grandes concentrations dans le placenta des grossesses prééclamptiques. Parallèlement, l’expression génique de certaines phospholipases A₂ est plus élevée dans le placenta en prééclampsie que chez les contrôles. En résumé, une augmentation des F₂-isoprostanes à effet vasoconstricteur, additionné à une augmentation de l’expression génique du récepteur au thromboxane A₂, pourraient jouer un rôle important dans l’hypertension locale placentaire en cas de prééclampsie.
Preeclampsia is a complex disorder during pregnancy. It is characterized by hypertension and proteinuria detectable after twenty weeks of gestation. An abnormal placental development/invasion is believed to be the first step of the pathophysiology. Preeclampsia is associated with an hypoxic condition, oxidative stress and the deregulation of polyunsaturated fatty acid synthesis and transfer to the growing fetus. Lipid peroxidation of arachidonic acid, an omega-6 fatty acid, lead potentially to the formation of sixty-four isomers of F₂-isoprostanes. F₂-isoprostanes are reliable biomarkers of oxidative stress and some are vasoconstrictors when released from the phospholipids membranes by phospholipases A₂. I have studied intact and oxidized fatty acids liberated by phospholipases A₂ and the thromboxane A₂ pathways in the placenta of normotensives and preeclamptic placentas. We have observed that plasmalogen, a sub-class of phospholipids enriched in polyunsaturated fatty acids, is elevated in the placenta of preeclamptic pregnancies. Furthermore, concentration of free F₂-isoprostanes is higher in preeclamptic placentas compared to controls. The latter was accompanied by elevated mRNA expression of specific phospholipases A₂ in preeclamptic placentas when compared to normotensive controls. In brief, elevated levels of free F₂-isoprostanes in addition to higher expression of thromboxane A₂ receptors could be involved in the local placental hypertension in preeclampsia.

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19

Schwedhelm, Edzard. "Isoprostane und 3-Nitrotyrosin als neue Indexparameter des oxidativen Stresses in vivo Analytik, Bildung, Metabolismus und biologische Bedeutung /." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=961131292.

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20

González, Luis Gema Esther. "Efecto de los isoprostanos en la reactividad vascular pulmonar y sistémica durante el período neonatal." Doctoral thesis, Universitat de Barcelona, 2005. http://hdl.handle.net/10803/2465.

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INTRODUCCIÓN: Los isoprostanos son compuestos similares a las Prostaglandinas (PGs) que se producen mediante una peroxidación no enzimática del ácido araquidónico inducida por radicales libres (Roberts & Morrow, 1997; Morrow y cols., 1999). Debido a su semejanza estructural con las PGs, se postula que no sean simples marcadores de la peroxidación lipídica, sino que también posean actividad específica. Se ha investigado la función biológica de los isoprostanos en animales adultos, en donde ejercen un efecto dual de predominio vasoconstrictor a nivel pulmonar y coronario. Sin embargo son muy pocos los referentes en este campo durante el período neonatal.

OBJETIVOS: 1.- Estudiar los efectos contráctiles y relajantes de diversos isoprostanos sobre vasos pulmonares y sistémicos de lechones recién nacidos (12-24 h) comparado con lechones de 2 semanas (15-18 días). 2.- Dilucidar los mecanismos de transducción de las respuestas vasculares a los isoprostanos en estos tejidos.

ANIMALES DE EXPERIMENTACION, MATERIAL Y MÉTODOS: Se estudió las respuestas contráctil y relajante de algunos isoprostanos (8-iso PGE1, 8-iso PGE2, 8-iso PGF1α, 8-iso PGF1β, 8-iso PGF2α, 8-iso PGF2β) y del mimético del tromboxano A2 -U46619- usando para ello el miógrafo mediante la técnica del baño de órganos. Se utilizaron anillos vasculares de la tercera rama de la arteria pulmonar (AP) y de la vena pulmonar (VP), del tronco principal de la arteria mesentérica (AM) y de la coronaria descendente anterior izquierda (AC).

RRESULTADOS:
- Contracción: Los isoprostanos producen una potente vasoconstricción dependiente de la concentración en AP, VP y AM (magnitudes 1,5-2 veces superiores a la respuesta de KCl 62,5 mM), pero ésta resulta ser muy inferior a la vasoconstricción desarrollada por U46619. La AP del lechón recién nacido resulta ser más sensible a la acción de 8-iso PGE2, 8-iso PGF1α, 8-iso PGF1β y 8-iso PGF2β que la AP del lechón de 2 semanas, sin que se observe un patrón ontogénico claro para el resto de los compuestos. La VP del recién nacido resulta más sensible a la acción de 8-iso PGE2 y 8-iso PGF1α y la AM del recién nacido a la acción 8-iso PGE2, 8-iso PGF1α, 8-iso PGF2α y 8-iso PGF2β que los correspondientes vasos de los animales de 2 semanas. La respuesta contráctil de todos los isoprostanos y del U46619 se revierte por SQ 29,548 (antagonista del receptor del tromboxano A2 -TP-), lo que indica que indica que la respuesta mediada por los isoprostanos implica al receptor TP. La contracción mediada por los isoprostanos se reduce en presencia de inhibidores de la tirosina cinasa (genisteína) y de la Rho cinasa (Y 27632 e hidroxifasudilo) pero no en presencia de inhibidores de la proteína cinasa C (queleritrina), de la cinasa de la proteína activadora del mitógeno (PD 98059) o de la p-38 cinasa (SB 203580).
-Relajación: 8-iso PGE2 induce una relajación en AP de lechones de dos semanas precontraídas con U46619 (máxima 60.1±8,7%) superior a la obtenida tras precontraer la AP con ET-1 en presencia de SQ 29,548 o en AC precontraídas con U46619. A diferencia de otros vasos, se observa también efecto relajante en AC para los siguientes isoprostanos: 8-iso PGE1 y 8-iso PGF2α. La relajación mediada por 8-iso PGE2 en la AP se redujo en presencia del inhibidor de la óxido nítrico sintetasa (L-NAME) y del inhibidor de la guanilato ciclasa soluble (ODQ). El Misoprostol, la PGE1 y la PGE2 indujeron relajación en la AP, pero no lo hicieron ni la PGD2 ni el iloprost.

CONCLUSIONES: 1.- Los isoprostanos tienen efectos contráctiles, los cuales son mayores en el recién nacido y se median por el receptor TP acoplado a la tirosina cinasa y Rho cinasa. 2.- Los isoprostanos tienen efectos relajantes que son mayores en animales de 2 semanas y que se median a través de la vía NO-GMPc.
"Effects of Isoprostanes in Pulmonary and Sistemic Vascular Reactivity during Neonatal Period".

BACKGROUND: Isoprostanes are prostaglandin (PG)-like compounds produced non enzymatically by free radical-catalyzed peroxidation of arachidonic acid. The vascular effects of these compounds in neonatal vasculature are poorly known.

OBJECTIVE: We aimed to study the effects of several E-ring and F-ring isoprostanes on mechanical activity in pulmonary arteries (PA), pulmonary veins (PV) and in mesenteric arteries (MA) from newborn and 2-week-old piglets.

DESIGN/METHODS: The contractile and relaxant responses to 8-iso PGE1, 8-iso PGE2, 8-iso PGF1α, 8-iso PGF1β, 8-iso PGF2α, 8-iso PGF2β, and the thromboxane A2 mimetic U46619 were studied using organ bath techniques.

RESULTS: Isoprostanes produced powerful concentration-dependent contractions of PA, PV and MA. Neonatal PA were more sensitive to 8-iso PGE2, 8-iso PGF1α, 8-iso PGF1β and 8-iso PGF2β than 2- week-old PA, but a clear ontogenic pattern was not observed for the rest of the compounds. Neonatal PV were more sensitive to 8-iso PGE2 and 8-iso PGF1α, and neonatal MA were more sensitive to 8-iso PGE2, 8-iso PGF1α, 8-iso PGF2α and 8-iso PGF2β than the corresponding 2-week-old vessels. The sensitivity to U46619-decraesed with postnatal age in MA but did not change in PA and PV. The contractile responses to all the isoprostanes and to U46619 were reverted by the thromboxane A2 receptor (TP) antagonist SQ 29,548. Moreover, isoprostanes-evoked contractions were blocked by inhibitors of tyrosine kinase (genistein) and Rho kinase (Y 27632 and hydroxy-fasudil). 8-iso-PGE2 induced modest dose-dependent relaxations (maximal relaxation of 60.1±8,7%) in 2-week-old PA. In CA, 8-iso PGE2 was the most potent vasodilator but relaxant responses evoked by 8-iso PGE1 y 8-iso PGF2α were also observed. 8-iso PGE2 -evoked PA relaxation was markedly impaired by the nitric oxide (NO) synthase inhibitor L-NAME and the soluble guanylate cyclase inhibitor ODQ. Misoprostol, PGE1 and PGE2 fully relaxed U46619-contracted PA, while no relaxation was observed in response to PGD2 or iloprost.

CONCLUSIONS: 1. Isoprostanes produce constriction of neonatal porcine pulmonary and mesenteric vascular smooth muscle which involve TP receptors coupled to tyrosine kinases and Rho kinases. 2. Isoprostanes produce modest or absent relaxant responses in piglet vascular smooth muscles. 8-iso-PGE2-evoked relaxation of piglet PA is likely to be mediated by NO.

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21

Mas, Emilie. "Isoprostanes : de la méthodologie à la clinique. Place potentielle dans l'exploration du diabète et des pathologies associées au vieillissement." Montpellier 1, 2005. http://www.theses.fr/2005MON13514.

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L'appréciation de l'importance du stress oxydant rend nécessaire l'utilisation de différents marqueurs. Des problèmes de sensibilité et de spécificité rendent ce choix délicat. La quantification des F2-isoprostanes, produits spécifiques de la peroxydation lipidique, représente une avancée importante pour disposer d'un outil clinique dans ce domaine. Nous avons développé des techniques de dosages immunologiques et des techniques de spectrométrie de masse. Ces techniques ont été appliquées pour évaluer la place du stress oxydant dans des situations cliniques. Tout d'abord pour évaluer l'effet d'une supplémentation en extrait hydrosoluble d'huile d'olive riche en hydroxytyrosol (HT) chez des patients diabétiques de type 1 sans complications vasculaires. Nous avons mis en évidence une diminution de la production de TXB2 impliqué dans l'agrégation plaquettaire et par conséquent un intérêt pour la prévention des complications vasculaires. Toutefois le dosage des F2-Isoprostanes ne montre pas d'effet antioxydant. Nous nous sommes ensuite intéressés à la place de l'hyperglycémie chez des patients diabétiques de type 2. La production des F2-Isoprostanes urinaires est corrélée à l'hyperglycémie post prandiale et plus encore aux fluctuations de glucose. Ces résultats suggèrent que la prise en charge de ces patients doit tenir compte à la fois des hyperglycémies chronique et post-prandiale mais aussi des variations de glucose. Dans un deuxième axe, nous nous sommes intéressés aux relations entre le stress oxydant, le vieillissement et la maladie d'Alzheimer. L'Apolipoprotéine E4, facteur de risque de la maladie d'Alzheimer est une cible préférentielle du stress oxydant. Il y a des discordances entre le résultat du génotypage et du phénotypage qui sont en partie attribuées à des dommages oxydatifs. Nous avons ensuite exploré les interactions entre le métabolisme lipidique, les antioxydants lipophiles et le polymorphisme de l'ApoE. Nos résultats montrent la disparition de l'effet hypercholestérolémiant de l'Apo E4 chez le DTA avec conservation du rapport vitamine E/lipides. Cette dysrégulation de l'homéostasie du CT observée au niveau systémique pourrait être présente dans le cerveau. Une supplémentation en antioxydant lipophile peut être envisager pour augmenter les rapports antioxydants lipophiles/lipides et favoriser l'incorporation cérébrale. Dans cette perspective, nous avons développé un projet de supplémentation chez des volontaires sains âgés pour évaluer l'impact d'un traitement antioxydant (vitamine E/C ou Ginkgo biloba) vs placebo. Les résultats de cette étude suggèrent que l'effet d'une supplémentation en antioxydant ne peut être évalué biologiquement qu'en présence d'un stress oxydant.

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22

Cracowski, Jean-Luc. "Modulation de la réactivité vasculaire humaine par des agonistes des récepteurs TP : thromboxane A2 et isoprostanes." Université Joseph Fourier (Grenoble), 2000. http://www.theses.fr/2000GRE18006.

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23

Flores, Meneses Lilliam. "Estrés oxidativo y fibrogénesis en la diabetes mellitus tipo 1: Influencia del control glucémico y del consumo de tabaco." Doctoral thesis, Universitat de Barcelona, 2005. http://hdl.handle.net/10803/2215.

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La base de esta tesis ha sido estudiar el efecto de dos noxas, la hiperglucemia y el consumo de tabaco, sobre las concentraciones de isoprostanos (F2-IsoPs), como expresión de estrés oxidativo (EO) y del factor transformador de crecimiento beta-1 (TGF-beta-1), como marcador de fibrogénesis, que son dos vías metabólicas estrechamente asociadas al desarrollo de las complicaciones crónicas de la diabetes mellitus (DM). Durante el diseño de esta tesis, la información que existía respecto a la modulación de ambas vías patogénicas era escasa y se centraba en fases avanzadas de la enfermedad. Valorar el EO y la fibrogénesis al inicio de la DM nos permitía analizar de forma específica el papel de la hiperglucemia, pero también nos posibilitaba describir su actividad en una fase de la enfermedad hasta ahora no estudiada. El consumo de tabaco es otro factor de riesgo definido para el desarrollo de las complicaciones crónicas de la DM de creciente interés clínico y del cual no existe información en pacientes con DM respecto a su posible efecto sobre los factores analizados en este trabajo.
Los resultados de este estudio demuestran que al inicio clínico de la DM1, las concentraciones de F2-IsoPs y de TGF-beta-1 ya están aumentadas. Observamos además que en el caso del EO ésta elevación es dependiente de la hiperglucemia, tal como lo indica el hecho de que sus valores disminuyen un 27% a las 12 semanas de iniciar el tratamiento con insulina y de mejorar el control metabólico.
Cuando evaluamos el efecto del control glucémico sobre los niveles de TGF-beta-1, observamos que a pesar de la importante mejoría del control glucémico obtenida en este estudio tras el inicio del tratamiento con insulina, estos niveles no se modificaron en ningún momento a lo largo del estudio. Este hecho nos sorprendió, debido a las evidencias existentes de que la hiperglucemia incrementa la actividad del TGF-beta-1, y, por tanto, era de esperar que la mejoría del control glucémico disminuyera su actividad. Esto nos hizo hipotetizar que en está fase de la DM1, la producción de TGF-beta-1 no está exclusivamente asociada al efecto estimulante de la hiperglucemia. El reciente conocimiento del papel de esta citocina en la modulación de la función celular inmune, permite plantear que estos niveles elevados de TGF-beta-1 probablemente estén relacionados con la actividad del proceso inmune implicado en la patogénesis de la enfermedad. Por lo que, el modelo clínico utilizado para valorar el efecto de la hiperglucemia sobre la fibrogénesis no nos permitió extraer conclusiones definitivas.
Por otra parte, se confirmó que el consumo de tabaco estimula directamente la actividad de ambas vías patogénicas implicadas en la patogénesis de las complicaciones crónicas. Explicando así, las numerosas evidencias epidemiológicas de la asociación entre el consumo de tabaco, el desarrollo y la progresión acelerada, con un peor pronóstico de las complicaciones crónicas en los sujetos con DM1 fumadores. Este resultado es de relevancia clínica ya que aporta más argumentos para insistir a los sujetos con DM1 fumadores a abandonar este hábito perjudicial.
"Oxidative stress and fibrogenesis in Type 1 diabetes mellitus: Effect of glycemic control and cigarette smoking"

The aim of this thesis was to study the effects of hyperglycemia and smoking on isoprostane concentrations (F2-IsoPs) which express oxidative stress (OS) and the transforming growth factor beta 1 (TGFb1) a marker of fibrogenesis. These two metabolic pathways are closely associated with the development of chronic complications in diabetes mellitus (DM).
Prior to this thesis information on the modulation of both pathogenic pathways was scarce and was focus on advanced phases of the disease. Evaluation of OS and fibrogenesis at the onset of DM allows the role of hyperglycemia to be specifically analysed and also makes it possible to describe its activity in a phase of the disease which, to date, has not been studied. Smoking is another risk factor for the development of chronic complications in DM which has gained increasing clinical interest. Moreover, no study has been performed in patients with DM concerning the possible effects on the factor analysed in this thesis.
The findings of this study demonstrate the both OS and fibrogenesis are already increased in early phases of DM and there is a direct relationship between hyperglycemia and OS. At the onset of type 1 DM we found the F2-IsoPs was already raised and this elevation was dependent on hyperglycemia shown by a 27 % decrease in the initial values 12 weeks after initiating insulin treatment and improving metabolic control.
When we evaluated the effect of glycemic control on TGFb1 level we found that despite an important improvement in glycemic control following the initiation of insulin treatment these levels were not modified at any time during the study. This finding was unexpected due to reports showing that hyperglycemia increases the activity of TGFb1 and thus we expected an improvement in glycemic control to reduce its activity. We therefore, hypothesized the in this phase of type 1 DM the production of TGFb1 is not exclusively associated with the stimulating effect of hyperglycemia. The recent description of the role of this cytokine in the modulation of immune cell function suggests that these elevated levels of TGFb1 are probably related to the activity of the immune process involved in the pathogenesis of this disease. Thus, the clinical model used to evaluate the effect of hyperglycemia on fibrogenesis has not allowed definitive conclusions to be drawn.
On the other hand, tobacco consumption has also been found to directly stimulate the activity of both pathogenic routes involved in the pathogenesis of chronic complications, thereby explaining the numerous epidemiological evidence regarding the association between smoking, the development and accelerated progression, and the worse prognosis of the chronic complications in smokers with type 1 DM. This is of clinical relevance because of the additional arguments it provides for persuading type 1 DM smokers to give up this harmful habit.

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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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25

Szollas, Rosemary. "8-isoprostane levels in exhaled breath condensate of pregnant women compared to non-pregnant women; is there a baseline difference?" [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001606.

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Heinz, Jutta [Verfasser], and Rainer H. [Akademischer Betreuer] Böger. "Isoprostane, Phytoprostane, Nitroölsäuren und Eiöl als Modulatoren der Genexpression : Zusammenhang zwischen oxidativem Stress und Atherosklerose / Jutta Heinz. Betreuer: Rainer H. Böger." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2013. http://d-nb.info/1031280340/34.

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Akiki, Zeina. "Biological Markers For Chronic Obstructive Pulmonary Disease And Asthma." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS081/document.

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L’étude des marqueurs biologiques dans la broncho-pneumopathie chronique obstructive (BPCO) et l'asthme, deux maladies respiratoires chroniques affectant des millions de personnes dans le monde, pourrait améliorer leur diagnostic, leur traitement et leur prévention.Cette thèse comprend deux parties. La première visait à évaluer l'association entre un marqueur spécifique des poumons, la protéine surfactant D (SP-D) sérique, et la BPCO, et à trouver un seuil de SP-D capable de discriminer les patients BPCO des témoins. Elle a été réalisée dans le cadre d’une étude cas-témoin au Liban incluant des patients BPCO (n=90), des asthmatiques (n=124) et des témoins (n=180). La deuxième partie visait à évaluer les associations chez les adultes des marqueurs de l’inflammation systémique (protéine C-réactive ultra-sensible, hs-CRP (n=252), et des cytokines (n=283)) et des marqueurs de dommages dus au stress oxydant (8-isoprostanes 8-IsoPs (n=258) du condensat de l’air exhalé) avec les phénotypes de l’asthme.Elle a été réalisée dans le cadre de l'étude épidémiologique longitudinale Française des facteurs génétiques et environnementaux de l'asthme (EGEA).Les résultats ont montré que les niveaux de SP-D sériques étaient associés positivement avec la BPCO et des seuils des niveaux de SP-D chez ces patients ont été identifiés avec d'excellentes valeurs discriminantes. Dans EGEA, aucune association n'a été trouvée entre les niveaux de hs-CRP sériques et le contrôle de l’asthme. Des profils de cytokines sériques (identifiés par analyse en composante principale) avec des niveaux élevés d’interleukine(IL)-1Ra et d’IL-10 ont été associés avec moins de crises d'asthme et un risque plus faible d'un mauvais contrôle de l'asthme sept ans plus tard. Les résultats des analyses préliminaires sur les associations entre les niveaux de 8-IsoPs et les phénotypes de l'asthme sont également présentés.Globalement, ces résultats ont montré l'utilité d'étudier les marqueurs biologiques en lien avec la BPCO et l'asthme
Studying the biological markers in chronic obstructive pulmonary disease (COPD) and asthma, two chronic respiratory diseases affecting millions of individuals around the world, could improve their diagnosis, their treatment and their prevention.This thesis includes two parts. The first aimed to assess the association between a lung-specific biomarker, serum Surfactant Protein D (SP-D), and COPD, and to find cut-off points able to discriminate COPD patients from controls using SP-D levels. It was performed in a case-control study in Lebanon including COPD (n=90) and asthma patients (n=124) and controls (n=180). The second part aimed to assess the cross-sectional and longitudinal associations in adults for systemic inflammatory biomarkers (high sensitivity C reactive protein hs-CRP (n=252) and cytokines (n=283) as well as biomarkers of damage due to oxidative stress (8-Isoprostanes 8-IsoPs (n=258) from the exhaled breath condensate) and asthma outcomes.It was performed in the French longitudinal epidemiological study on the genetics and environmental factors of asthma (EGEA).Results showed that serum SP-D levels were positively associated with COPD and thresholds for SP-D levels in these patients were identified with excellent discriminant values. In EGEA, no association was found between serum hs-CRP levels and asthma control. Serum cytokine profiles (identified by principal component analysis) with high levels of interleukin (IL)-1Ra and IL-10 were associated with less asthma attacks and lower risk of poor asthma control in adults seven years later. The results of the preliminary analyses on the associations between the levels of 8-IsoPs and asthma outcomes are also presented.Overall, these results have shown the usefulness of studying the biological markers related to COPD and asthma

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Junge, Tanja. "Untersuchung von 8-Isoprostanen als Markersubstanzen für oxidativen Stress bei Patienten mit atopischem Ekzem und anderen Erkrankungen des atopischen Formenkreises." kostenfrei, 2008. http://mediatum2.ub.tum.de/doc/653399/653399.pdf.

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Kurti, Stephanie P. "The impact of lifestyle, age, and sex on systemic and airway inflammation and oxidative stress." Diss., Kansas State University, 2017. http://hdl.handle.net/2097/35294.

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Doctor of Philosophy
Department of Kinesiology
Craig A. Harms
The overall aim of this dissertation was to determine the impact of lifestyle (i.e. habitual and acute physical activity and diet), age, and sex on systemic and airway inflammation and oxidative stress. In study 1 (Chapter 2) we examined the impact of habitual physical activity level on the post-prandial airway inflammatory response following an acute bout of moderate intensity exercise. Results indicated that the mean exhaled nitric oxide (eNO; marker of airway inflammation) response increased for all groups at two hours post high-fat meal (HFM) (~6%) and returned to baseline by four hours post-HFM. However, there was a varying eNO response from baseline to four hours in the group that exercised in the post-prandial period compared to the group that remained sedentary. These findings suggest airway inflammation occurs after a HFM when exercise is performed in the post-prandial period, regardless of habitual physical activity level. In study 2 (Chapter 3) we investigated the post-prandial oxidative stress response to meals of varying calories and fat. Specifically, we assessed the post-prandial airway and systemic 8-isoprostane (a marker of oxidative stress) responses to meals with moderate-fat (8.5 kcal/kg of bodyweight) and high-fat content (17 kcal/kg of bodyweight) from baseline to six hours post-meal in a randomized crossover design. This study revealed that systemic 8-isoprostane increased from baseline to six hours post-meal (38.3%), but there was no difference between the moderate-fat meal (MFM) and HFM conditions. There were no changes in airway 8-isoprostane from baseline to six hours post-MFM or HFM, or between the MFM and HFM conditions. Lastly, in study 3 (Chapter 4), we were interested in examining 8-isoprostane responses in older adults, since 8-isoprostane has been reported to increase with age. Previous research also suggests that older women (OW) and older men (OM) have differences with regard to prevalence and severity of late-onset asthma. In this study, we sought to determine whether the airway 8-isoprostane response to a strenuous bout of exercise was different in OW compared to OM. A secondary aim was to determine whether post-exercise 8-isoprostane generation was correlated with decrements in lung function. Our results showed that the generation of 8-isoprostane from pre- to post-exercise increased ~74±77% in OW and decreased ~12±50% in OM. The decrease in 8-isoprostane generation was not correlated with improvements in lung function from pre- to post-exercise. These findings collectively contribute to the literature by enhancing our understanding of the impact of lifestyle factors, age and sex on modifying and potentially mitigating the risk of developing chronic diseases.

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Tolley, Jeffrey Ray. "Are Cardiovascular Disease Inflammatory Markers Elevated in Those with Nonspecific Chronic Musculoskeletal Pain Compared to Nonpain Case Controls?" BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/6309.

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CONTEXT: Recent studies have considered the role of inflammation in the development of both cardiovascular disease (CVD) and musculoskeletal conditions, such as rheumatoid arthritis. Studies suggest that inflammation plays a significant role in the development of cardiovascular disease. In conditions of chronic pain, as with rheumatoid arthritis, inflammation has also been noted through elevated levels of inflammatory markers. There are currently no studies that examine the possible connection between inflammatory markers related to increased risk of cardiovascular disease and nonspecific chronic musculoskeletal pain (NCMP). OBJECTIVE: The purpose of this study was to determine whether urinary levels of microalbumin (MA) and F2-isoprostanes (F2-isoPs), inflammatory biomarkers associated with increased CVD risk, are elevated in persons with NCMP compared to nonpain case controls. NCMP refers to pain present for more than 3 days per week and for more than 12 weeks. This type of pain is not due to injury but is associated with interference of normal function. DESIGN: Nonrandomized observational study. METHODS: A cross-sectional study with 120 participants (60 pain subjects, 60 nonpain case-controls). A single first-morning void urine sample was collected from each subject. Urine specific gravity and total volume were measured and then a sample was sent to a lab for analysis of MA and F2-isoPs. Inflammatory biomarker levels in the pain and nonpain groups were compared. RESULTS: There were no significant differences in F2-isoPs levels between the chronic pain group (0.65ng/mg ± 0.05) and the nonpain group (0.80ng/mg ± 0.07) (95% CI (-0.32, 0.03)). However, MA levels were significantly higher in the chronic pain group (2.41mg/g ± 0.24) compared to the nonpain group (1.88mg/g ± 0.14) (95% CI (0.34, 1.68)). MACR levels were also significantly higher in the chronic pain group (2.07mg/g ± 0.31) compared to the nonpain group (1.14mg/g ± 0.14) (95% CI (0.32, 1.64)). CONCLUSION: These findings suggest a possible link between at least one inflammatory marker (microalbumin) and NCMP. This in turn allows for a limited but reasonable inference that NCMP may be a risk factor for cardiovascular disease, mediated through the MA inflammatory biomarker. Further research is needed to more fully understand the possible connection between NCMP and CVD.

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Larose, Jessica. "Analyse des isomères de F2-isoprostanes par chromatographie liquide couplée à la spectrométrie de masse dans la circulation maternelle en fin de grossesse." Master's thesis, Université Laval, 2013. http://hdl.handle.net/20.500.11794/25559.

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Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2013-2014.
Un stress oxydatif survient lorsqu’il y a surproduction de dérivés actifs de l’oxygène par rapport aux défenses antioxydantes. Ce déséquilibre est associé, entre autres, à la prééclampsie, une pathologie de la grossesse. Les F2-isoprostanes regroupent soixante-quatre isomères issus de la peroxydation de l’acide arachidonique. Ceux-ci sont reconnus comme étant les biomarqueurs les plus fiables du stress oxydatif in vivo. Une méthode d’analyse par chromatographie liquide couplée à la spectrométrie de masse en tandem pour le dosage de sept isomères de F2-isoprostanes dans des échantillons de plasma, de sang et de membranes érythrocytaires a été mise au point et validée. Les F2-isoprostanes dans le plasma ont été corrélés positivement avec plusieurs acides gras trans plasmatiques au troisième trimestre de la grossesse. Contre toute attente, les F2-isoprostanes du plasma, du sang et des membranes érythrocytaires sont moins abondants en prééclampsie par rapport aux contrôles en fin de grossesse.
An oxidative stress is defined as an imbalance between the production of reactive oxygen species and antioxidant defenses of the organism. This imbalance has been associated with preeclampsia, a pathology of the mid-to-late pregnancy. Peroxidation of arachidonic acid generates sixty-four isomers of F2-isoprostanes. The latter are recognized as the most reliable biomarkers of oxidative stress in vivo. A method using liquid chromatography tandem mass spectrometry (HPLC-MS/MS) for the determination of seven isomers of F2-isoprostanes in plasma samples, whole blood and erythrocyte membranes has been developed and validated. The F2-isoprostanes correlated positively with several trans fatty acids in plasma at end of the pregnancy. Unexpectedly, F2-isoprostanes were less abundant in preeclampsia than in control pregnancies at the third trimester.

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Gerstner, Anemone [Verfasser], and Rolf [Akademischer Betreuer] Nüsing. "Studien zur Untersuchung von F2-Isoprostanen und 8-epi-PGF2α als Marker für oxidativen Stress bei Typ 1 Diabetes / Anemone Gerstner. Betreuer: Rolf Nüsing." Marburg : Philipps-Universität Marburg, 2014. http://d-nb.info/1051934338/34.

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Werner, Matthias Nicolai Takeshi [Verfasser], and Edzard [Akademischer Betreuer] Schwedhelm. "Isoprostane und der Thromboxan-A2-Rezeptor (TP) : in vitro Untersuchungen in der TP-/- Maus und in vivo Korrelation mit dem Akuten Koronarsyndrom / Matthias Nicolai Takeshi Werner. Betreuer: Edzard Schwedhelm." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2015. http://d-nb.info/1073248356/34.

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Tan, Rachel Hsing Hsing. "Biomarkers of oxidative stress and inflammation in biological samples collected from recurrent airway obstruction (RAO)-affected horses and their controls." Thesis, Virginia Tech, 2008. http://hdl.handle.net/10919/32819.

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Multiple biomarkers of oxidative stress have been measured and used in human medicine to diagnose and monitor airway disease. The purpose of the study was to determine if similar relationships existed between inflammatory and oxidative stress biomarkers in exhaled breath condensate (EBC), bronchoalveolar lavage fluid (BALF), red blood cells, white blood cells, and plasma; and cytokine expression in airway inflammatory cells and mucosal biopsies of RAO-affected horses and their controls. Sixteen horses in pairs were used: 8 non-RAO-affected (controls) and 8 RAO-affected horses. Samples from all horses were collected at remission (S1), during environmental challenge (S2) and at recovery (S3). RAO-affected horses had significant alterations in cellular glutathione peroxidase (cGPx) activity, ascorbic acid and pH in a number of biological samples. Concentrations of 8-isoprostanes, isofurans, amino acids and mRNA expression of interleukin 4 (IL4), gamma interferon (INFÎ³), inducible nitric oxide synthase (iNOS), extracellular glutathione peroxidase (GPx-3), and cytosolic superoxide dismutase (SOD-1) were not significantly different or were at the limits of detection. Conductivity was measured and assessed as a potential correctional factor for respiratory fluid dilution. The alterations in biomarker concentrations demonstrate that oxidative stress is an important component of airway inflammation in RAO-affected horses. Further research is warranted in the use of biomarkers and the effects of dietary interventions.
Master of Science

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Lipcsey, Miklós. "Pathophysiological, Inflammatory and Haemostatic Responses to Various Endotoxaemic Patterns : An Experimental Study in the Pig." Doctoral thesis, Uppsala University, Department of Surgical Sciences, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7237.

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Septic shock is frequently seen in intensive care units and is associated with significant mortality. Endotoxin – a major mediator of the pathophysiologic responses – is released during lysis of Gram-negative bacteria. These responses can be mimicked in the endotoxaemic pig.

This thesis focuses on the following topics: the inflammatory and pathophysiological responses to various endotoxin doses and infusion patterns; covariations between endotoxin induced inflammatory and pathophysiological responses; whether the biological effects of endotoxin can be modulated by clopidogrel and whether tobramycin or ceftazidime reduce plasma cytokine levels.

Endotoxin induced linear log-log cytokine and F2-isoprostane responses. Leukocyte and platelet responses, pulmonary compliance, circulatory variables as well as indicators of plasma leakage and hypoperfusion exhibited log-linear responses to the endotoxin dose. Biological responses to endotoxaemia such as inflammation, hypotension, hypoperfusion and organ dysfunction were more expressed when the organism was exposed to endotoxin at a higher rate. These results may facilitate the possibility to choose relevant endotoxin administration, when experiments are set up in order to evaluate certain responses to endotoxaemia.

Correlation studies between cytokines, leukocytes, platelets and the endotoxin dose were in agreement with the well-known ability of endotoxin to induce cytokine expression and to activate both primary haemostasis and leukocytes. Free radical mediated lipid peroxidation and COX-mediated inflammation correlated to cytokine expression and organ dysfunction in endotoxaemic shock.

Endotoxaemic pigs pretreated with clopidogrel, exhibited a trend towards less expressed deterioration of renal function, although blocking of ADP-induced primary haemostasis is not a key mediator of endotoxin induced deterioration of renal function.

Tobramycin did not neutralise the biological effects of endotoxin or the plasma levels of endotoxin, suggesting that these antibiotics do not bind to endotoxin.

Reduction in IL-6 was greater in pigs treated with ceftazidime and tobramycin as compared with those given saline, indicating a possible anti-inflammatory effect of both antibiotics.

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Nozari, Ala. "Experimental cardiopulmonary cerebral resuscitation : A study of cerebral perfusion with special reference to the postresuscitation disturbances." Doctoral thesis, Uppsala University, Department of Surgical Sciences, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-459.

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Ischemic neuronal injury continues to be a major delimiting factor in achieving successful clinical outcomesafter resuscitation from cardiac arrest. In this thesis, a pig model of cardiopulmonary resuscitation (CPR) wasused to address the effects of different interventions on cerebral blood flow and oxygenation during CPR and theinitial postresuscitation period. A novel technique is presented to quantify the reperfusion oxidative injury.

Maximization of cerebral blood flow during CPR by open-chest cardiac compression, continuous aortic balloon occlusion, and intra-aortic administration of hypertonic saline-dextran (HSD) did not ameliorate thepostresuscitation hypoperfusion or improve the cerebral oxygen extraction ratio or tissue pH. These findings disaffirm earlier studies suggesting that conserving brain viability after global ischemia is mostly a question ofmaintaining high perfusion pressure.

Despite an increased cerebral perfusion pressure during CPR, intra-aortic administered epinephrineabove the aortic balloon occlusion did not further improve cerebral blood flow and oxygenation. This findingmay indicate adverse effects of epinephrine on cerebral vascular beds, possibly induced by a relatively highconcentration of epinephrine when administered above the site for aortic balloon occlusion.

The IV administration of equipotent doses of epinephrine or vasopressin during CPR resulted incomparable hemodynamic changes. The peak increase in cerebral cortical blood flow, however, was reachedapproximately 30 sec later by vasopressin. Furthermore, the second bolus of vasopressin during CPR did notaugment cerebral perfusion, whereas epinephrine did. Consequently, reports suggesting that vasopressin issuperior to epinephrine with respect to its effects on central hemodynamics and vital organ blood flow may bebiased by the pharmacodynamic differences between the drugs, depending on the time point at which blood flowmeasurements are performed.

In comparison with IV vasopressin, vasopressin administered above the aortic balloon occlusion resulted in a significant increase in cerebral perfusion pressure during CPR, but not after restoration of spontaneous circulation (ROSC). Cerebral cortical blood flow was, however, not improved during CPR, whereas a significant increase was recorded after ROSC. Relatively higher concentrations of vasopressin above the sitefor intra-aortic balloon occlusion may, therefore, predominantly induce cerebral cortical vasoconstriction duringCPR but induce vasodilatation after ROSC.

Assessment of oxidative stress or inflammation have been extremely difficult to attain. In our pig model of resuscitation, an association wasobserved between the duration of cardiac arrest and jugular bulb levels of 8-iso-PGF_2α, a major isoprostane and a novel index of oxidative injury. 8-iso-PGF_2α, and the prostaglandin 15-K-DH-PGF_2α, increased within 5 min after ROSC and remained so up to 2 h, indicating the interval of time during which cerebral reperfusion oxidative injury and inflammatory response may occur and are potentially preventable.

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Claeson, Bohnstedt Kristina. "Determination of biomarkers for lipid peroxidation and oxidative stress : Development of analytical techniques and methods." Doctoral thesis, Stockholm : Department of Analytical Chemistry, Stockholm University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-322.

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Palm, Maria. "Oxidative Stress, Angiogenesis and Inflammation in Normal Pregnancy and Postpartum." Doctoral thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-171165.

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The aims were to investigate oxidative stress (I), angiogenesis (II) and inflammation (III-IV) in healthy women during pregnancy and postpartum. Oxidative stress was estimated by measurement of 8-iso-PGF2α and the antioxidants α- and γ-tocopherol. The angiogenic factors PlGF, VEGF-A and the antiangiogenic factor sFlt1 were measured to estimate angiogenesis. PTX3, IL-6, TNF-α and a PGF2α metabolite were measured to estimate inflammation. Out of 52 included women, 15 had minor pregnancy complications and 37 were classified as normal. In study III data from all 52 women were used. For the other studies (I, II and IV) only data from the 37 women with normal pregnancy were used. Pregnancy was associated with increased levels of 8-iso-PGF2α with advancing gestational age. The median postpartum value corresponded to values observed in early gestation and a significant decrease was observed from late pregnancy to postpartum. Lipid-adjusted α- and γ-tocopherol levels decreased with advancing gestational age (I). PlGF increased from early pregnancy until weeks 29–30 and thereafter decreased until week 40. sFlt1 levels were relatively constant until weeks 29–30, when they increased, reaching a peak at weeks 39–40. Postpartum levels were low. The sFlt1:PlGF ratio decreased from weeks 9–12, was constantly low from weeks 19–20 to 37–38 and then increased to weeks 39–40. VEGF-A was detectable in only 8 % of the samples during pregnancy and in 64 % postpartum (II). There was a continuous increase of PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery (III). IL-6 increased throughout pregnancy and remained high postpartum. No change in TNF-α could be seen with advancing gestational age or postpartum. The PGF2α metabolite levels increased throughout pregnancy and decreased postpartum (IV). In conclusion, normal pregnancy is associated with mild oxidative stress and inflammation. This might have physiological effects for normal pregnancy development. By delineating how these mediators of oxidative stress, angiogenesis and inflammation fluctuate throughout normal pregnancy and postpartum, we have established a reference for studies of these factors in pregnancy complications.

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Wikström, Anna-Karin. "Biochemical and Epidemiological Studies of Early-Onset and Late-Onset Pre-Eclampsia." Doctoral thesis, Uppsala University, Department of Women's and Children's Health, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8279.

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Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease.

In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. (Paper I)

In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. (Paper II)

Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF_2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF_2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. (Papers III, V) There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. (Paper IV)

In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta.

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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 F_2α 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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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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Södergren, Eva. "Lipid peroxidation in vivo : Evaluation and application of methods for measurement." Doctoral thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1250.

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Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of ageing, but its measurement in vivo has been difficult. The aim of this thesis was to evaluate methods for measurement of lipid peroxidation in vivo that are suitable for clinical investigations, and to apply these methods in animal and human studies investigating basal conditions and situations associated with increased lipid peroxidation. The ferrous oxidation in xylenol orange assay for quantification of total plasma lipid hydroperoxides was re-evaluated regarding sample handling and storage. It was shown to be a useful tool for analyses of fresh but not stored plasma samples. A methodology for measurement of the total amount (sum of free and esterified) of an F2-isoprostane, 8-iso-prostaglandin F2α, in tissues using alkaline hydrolysis in combination with an existing radioimmunoassay was developed. High levels of 8-iso-prostaglandin F2α in rat liver tissue were quantified by this technique both at basal conditions and in an experimental model of increased lipid peroxidation induced by carbon tetrachloride. Supplementation with vitamin E to rats decreased both non-enzymatic and enzymatic lipid peroxidation as measured by 8-iso-prostaglandin F2α and a major prostaglandin F2α metabolite. This was verified both in the urine at basal conditions, and in the urine and liver tissue after carbon tetrachloride induced lipid peroxidation. In a randomised cross-over study in humans, a rapeseed oil-based diet with an increased proportion of easily oxidised polyunsaturated fatty acids was compared to a control diet rich in saturated fats. The rapeseed oil-based diet did not seem to increase the degree of lipid peroxidation in plasma and urine as measured by 8-iso-prostaglandin F2α, hydroperoxides and malondialdehyde, presumably due to a sufficient content of antioxidants in the rapeseed oil diet. In conclusion, the simultaneous measurement of several biomarkers of lipid peroxidation is a promising approach for future studies investigating the possible role of lipid peroxidation in vivo under basal conditions and in the pathology of diseases.

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Cederberg, Jonas. "Oxidative stress, antioxidative defence and outcome of gestation in experimental diabetic pregnancy." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-4960-3/.

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Smedman, Annika. "Milk Fat Intake and Conjugated Linoleic Acid (CLA) Supplementation : Dietary Markers and Associations to Clinical and Biochemical Characteristics." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4820.

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Mácová, Daniela. "Využití separačních technik ve spojení s hmotnostní spektrometrií pro stanovení environmentálně významných látek." Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2012. http://www.nusl.cz/ntk/nusl-233356.

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The identification of the hydrolysis and photodegradation products of flexible polyurethane foams (PUFs) with addition of biooriginated and biodegradable additive was the first topic of this dissertation work. Separation of polyurethane foam hydrolysis degradation products, designed for ecotoxicological tests, was managed by high-performance liquid chromatography coupled with mass spectrometry (HPLC/MS). The degradations product structure was elucidated by tandem mass spectrometry (MSn). PUF photodegradation products were obtained by exposure of materials by irradiation at 254 nm. Semi-volatile degradation products were isolated from the exposed polyurethane by n-hexane extraction; volatile compounds were collected by solid phase microextraction (SPME). Gas chromatography with mass spectrometry (GC/MS) and complete orthogonal tandem gas chromatography with mass spectrometry (GCxGC/TOF MS) was used for separation and identification of photodegradation products. The influence of the bio-filler on the character of degradation products and the possible effect of PUF degradation products on the environment was discussed at the end of this section. The determination of isoprostanes – markers of oxidative stress in tissues of beadlet anemone (Actinia equina) was the subject of the second topic. F2-isoprostanes were synthesized from the arachidonic acid. With thereby prepared isoprostanes the method of determination by liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) was developed and optimized. The isoprostane isolation process from the Actinia equina tissues was optimized with solid phase extraction (SPE). The resulting methodology was used to quantify isoprostanes in tissues of anemones, which were exposed to both moderate and high temperature changes. The temperature changes were used to initiate the oxidative stress in organisms. In addition, concentration levels of unknown compounds were also monitored. These unknown compounds were extracted from tissues together with F2-isoprostanes and their identity is discussed in this dissertation work too. The possibility of using isoprostane levels in the Anthozoa tissues for the oxidative stress monitoring is discussed in the conclusion of this work.

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Bjermo, Helena. "Dietary Fatty Acids and Inflammation : Observational and Interventional Studies." Doctoral thesis, Uppsala universitet, Klinisk nutrition och metabolism, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156074.

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Dietary fat quality influences the risk of type 2 diabetes and cardiovascular disease. A low-grade inflammation is suggested to contribute to the disease development, often accompanied by obesity. Whereas n-3 polyunsaturated fatty acids (PUFA) have been considered anti-inflammatory, n-6 PUFA have been proposed to act pro-inflammatory. Saturated fatty acids (SFA) act pro-inflammatory in vitro. This thesis aimed to investigate effects of different fatty acids on low-grade inflammation in observational and interventional studies. In Paper I and II, fatty acid composition in serum cholesterol esters was used as objective marker of dietary fat quality and related to serum C-reactive protein (CRP) and other circulating inflammatory markers in two population-based cohorts, conducted in middle-aged men and elderly men and women, respectively. In Paper III and IV, the impact of diets differing in fat quality on inflammation and oxidative stress was investigated in randomised controlled studies, in subjects with metabolic syndrome and abdominal obesity. In Paper I and II, a low proportion of linoleic acid (18:2 n-6) in serum was associated with higher CRP concentrations, indicating that a low intake of vegetable fats may be related to low-grade inflammation. High CRP concentrations were also associated with high proportions of palmitoleic (16:1) and oleic (18:1) acids and high stearoyl coenzymeA desaturase index, possibly reflecting altered fat metabolism and/or high SFA intake in this population. When comparing two high-fat diets rich in either saturated or monounsaturated fat, and two low-fat diets with or without long-chain n-3 PUFA supplementation during 12 weeks (Paper III), no differences in inflammation or oxidative stress markers were observed. Moreover, a 10-week intervention (Paper IV) with high linoleic acid intake showed no adverse effects on inflammation or oxidative stress. Instead, interleukin-1 receptor antagonist and tumor necrosis factor receptor-2 decreased after linoleic acid intake compared with a diet high in SFA. The results in this thesis indicate that dietary n-6 PUFA found in vegetable fats is associated with lower inflammation marker levels, and to some extent reduces systemic inflammation when compared with SFA. Supplementation of n-3 PUFA did not exert any systemic anti-inflammatory effects, maybe due to a relatively low dose.

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Daryani, Achraf. "Diet and Metabolic Risk Factors in Immigrant Women from the Middle East and Swedish-Born Women : A Cross-Sectional Study of Women from Iran, Turkey and Sweden." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7103.

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48

Kornobis-Chérot, Nathalie. "Évaluation méthodologique et clinique des marqueurs de l’atteinte pulmonaire dans l’air exhalé : comparaison de sujets présentant une pathologie respiratoire chronique et sujets témoins." Thesis, Lille 2, 2012. http://www.theses.fr/2012LIL2S013/document.

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Un accès direct et non invasif à la pathogénèse par l’évaluation de biomarqueurs volatils (FeNO) ou non volatils de l’air exhalé grâce à la méthode des condensats de l’air exhalé (EBC) est utile pour estimer précocement le degré d’atteinte pulmonaire en rapport avec une exposition professionnelle et surveiller son évolution en regard des mesures correctives mises en place. L’étude du NO exhalé (FeNO) est actuellement bien standardisée et l’augmentation exponentielle des publications concernant les EBC reflètent un intérêt croissant pour le diagnostic non invasif des atteintes pulmonaires. Les marqueurs étudiés dans l’air exhalé sont des produits de l'inflammation tels que le FeNO et les cytokines ainsi que des produits du stress oxydant incluant le peroxyde d'hydrogène, les produits de peroxydation lipidique (8-isoprostane, malondialdehyde) et les oxydes d'azote (NOx). S’agissant d’une technique d’exploration relativement récente, les modalités méthodologiques font encore l’objet de nombreux travaux, les premières recommandations internationales étant apparues en 2005. Les écueils méthodologiques sont nombreux et encore décrits dans la littérature en 2012. Ils concernent toutes les étapes du processus du recueil et d’analyses.Objectifs : L’objectif principal de notre recherche était dans un premier temps de développer la méthode des EBC pour l'étude des composés de l'air exhalé puis de détecter et quantifier des biomarqueurs tels que les protéines totales, les NOx et le 8-isoprostane dans les EBC d’une population d’adultes sains (n= 48) ou atteints de pathologies pulmonaires telles que l'asthme (n=24), la BPCO (n=20), la pneumopathie interstitielle diffuse (n=27) et la sclérodermie (n=27). L’objectif secondaire était la comparaison des niveaux de biomarqueurs dosés dans les EBC et du FeNO chez les sujets malades par rapport aux témoins.Résultats / Conclusion : Notre recherche, soutenue l’ANR et l’ANSES, a permis de standardiser la méthodologie de recueil et d’analyse des EBC avec une optimisation du système de recueil et de l’agent coatant pour la détermination de la concentration nécessaire et compatible avec les analyses. Nous maitrisons le dosage dans les EBC des biomarqueurs tels que les protéines, les NOx et le 8-isoprostane. D'autres biomarqueurs sont encore en cours d'étude tels que le malondialdehyde et les cytokines. Ce travail méthodologique, publié, a permit dans un second temps la détection (> à 95%) et la quantification de ces biomarqueurs dans les EBC des sujets sains et malades de notre population.Perspectives : La constitution des valeurs de référence pour les biomarqueurs dosés dans les EBC est nécessaire à l’interprétation des dosages chez les sujets malades. Il convient également de finaliser la standardisation de la mesure des cytokines et du malondialdehyde et d’explorer de nouveaux biomarqueurs produits lors du stress nitrosant tels que la 3-nitrotyrosine pour compléter les mécanismes physiopathologiques. Enfin le développement de cette méthode non invasive et peu contraignante apparait prometteuse en clinique médicale dans le suivi individuel de la maladie ou son traitement comme lors d’études épidémiologiques respiratoires dans des populations exposées professionnellement ou environnementalement. Dans ce cadre, l’étude de marqueurs d’exposition professionnelle tels que les métaux lourds dans les EBC est en cours de développement
The study of both volatile (FeNO) and non-volatile respiratory biomarkers using the method of exhaled breath condensates can be useful in medical surveillance of exposed workers, the early identification of respiratory diseases or in the monitoring of their development. Studies of exhaled NO (FeNO) is now well standardized and the exponential increase in publications on exhaled breath condensate (EBC) reflects growing interest in a non-invasive diagnosis of pulmonary diseases. The biomarkers studied are products of inflammation, such as FeNO and cytokines, and products of oxidative stress, including hydrogen peroxide (H202), products of lipid peroxydation (8-isoprostane, malondialdehyde) and nitrogen oxides. The first recommendation was published in 2005 but although many recent publications have applied this new method, numerous methodological pitfalls remain and still described in 2012. They concern all the stages of the collection to the analysis.Objectives: The main objective of this research was initially to develop the method of EBC for the study of compounds of exhaled air and then detect and quantify biomarkers such as total protein, NOx and 8-isoprostane in exhaled air in a population of healthy adults (n = 48) or patients with lung inflammatory diseases such as asthma (n = 24), COPD (n = 20), diffuse interstitial pneumonia (n = 27) and scleroderma (n = 27). The secondary objective was to compare levels of biomarkers measured in the EBC and FeNO in patients compared to controls.Results / conclusion: Our research, supported by ANR and ANSES, allowed to standardize the methodology of collection and analysis of EBC with a choice of the collection system and coating which must be effective and compatible with the analyzes. In EBC, we control the dosage of biomarkers such as proteins, NOx and 8-isoprostane. Other biomarkers are still being studied such as malondialdehyde and cytokines. This published methodological study, allowed in a second step the detection (> 95%) and quantification of these biomarkers in EBC of healthy patients in our population.Perspectives: This standardization is a key epidemiological requirement for the task force on the establishment of reference values and the publication of methodological guidelines so as to realize the promise of this approach for clinical studies of lung diseases. We have also to finish the development of biomarkers such as cytokines or malondialdehyde and to investigate new biomarkers to complete the pathophysiological mechanisms. Finally our objective is the widespread use of this noninvasive method in daily epidemiological studies on subjects with professional and/or environmental exposure. In this context, the study of markers of the toxic burden in the lungs such as heavy metals in the EBC is being developed

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Tseng, Hui Yun, and 曾惠筠. "A study of exhaled breath condensate 8-isoprostane and leukotrienes in human." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/11908145179547682713.

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碩士
長庚大學
臨床醫學研究所
99
Previous studies indicated that inflammatory mechanism of allergic airway diseases was related to oxidative stress. 8-isoprostane is the major biomarker of oxidative stress and cysteinyl leukotrienes (cys-LTs) is one of the important mediators in airway inflammation process. The purpose of this study was to evaluate the concentration distributions and seasonal variations of exhaled 8-isoprostane and cys-LTs in the children with allergic airway diseases and healthy subjects. Also, the analytical methods of EBC leukotriene B4 (LTB4) and leukotriene E4 (LTE4) in human were tried to establish in this study. Thirty four children with allergic airway diseases and 24 healthy controls were recruited from Taipei Chang Gung Memorial Hospital and primary schools in Taipei city, respectively. All the EBC 8-isoprostane and cys-LTs concentrations were analyzed by enzyme-linked immunoassay method. It was indicated that the median levels of EBC 8-isoprostane and cys-LTs in children with allergic rhinitis and comorbidity of asthma and allergic rhinitis were significantly higher than those in both asthmatic children and healthy controls. In addition, higher EBC 8-isoprostane and cys-LTs concentrations in children were found in summer and winter seasons. A significant correlation was found between EBC 8-isoprostane and cys-LTs levels. To establish the standard methods of EBC LTB4 and LTE4 using high-performance liquid chromatography (HPLC) coupled with ultraviolet spectroscopy, sixty healthy controls were recruited from Chang Gung University in the study . It was found that the LTB4 and LTE4 concentrations in all the EBC samples were under detection limits (LTB4: 1 ng/μL; LTE4: 20 ng/μL). The total amount of EBC LTB4 was 2700 pg in the pooled specimen with 60 EBC samples, but the LTE4 level was undetectable in the pooled specimen.

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Olmsted, Alexandra. "Sperm Mitochondrial Copy Number and Associations with Oxidative Stress and Phthalate Metabolites in Male Partners Undergoing Assisted Reproductive Technologies." 2017. https://scholarworks.umass.edu/masters_theses_2/547.

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INTRODUCTION Phthalates, a chemical class of plasticizers, are ubiquitous in the environment and recognized as endocrine disrupting compounds (EDCs). Recent data suggest that oxidative stress is a potential mediator of poor male reproductive health associated with phthalate exposure. Mitochondria are implicated in the production of excess oxidative stress and sperm mitochondrial copy number (MtCopy) and deletions (MtDeletion) have been linked with male infertility. However, little is known about the relationship of these mitochondrial biomarkers in sperm with phthalate exposure and oxidative stress. OBJECTIVES To examine associations of urinary phthalate metabolites and isoprostane concentrations on sperm MtCopy and MtDeletions in male partners undergoing assisted reproductive technologies (ART). METHODS A total of (n=97) sperm samples were collected from male partners undergoing ART at Baystate Medical Center, in Springfield, MA from 2014 to 2016 as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Seventeen urinary phthalate metabolites (n=103) were analyzed by the Centers for Disease Control using tandem mass spectrometry. 15-F2t-Isoprostane (n=101) was measured using a competitive enzyme-linked immonsorbent assay in urine of male individuals. A triplex Taqman probe-based qPCR method was developed for relative quantification of genomic DNA, MtCopy and MtDeletions. Multivariable linear or logistic regression was employed to examine associations with age, BMI, batch and current smoking status with each outcome to determine confounders used for adjustment. RESULTS Quartiles of MtCopy and MtDeletion were positively associated with the odds of male infertility (p for trend < .0001 and 0.007, respectively). Urinary metabolite concentrations of MCNP displayed a positive association with MtCopy (β=1.56; p =0.03). Urinary MEHP concentrations were positively associated with MtDeletion in only infertile individuals (n=30) (β = 0.075; p = 0.006). Urinary isoprostane concentration was not associated with MtCopy or MtDeletion, but was associated with seven phthalate metabolite concentrations (MEOHP, MEHHP, MBzP, MHBP, MiBP, and MHiBP). CONCLUSIONS To our knowledge, this is the first study to investigate the relationship between sperm MtCopy and MtDeletion with oxidative stress and phthalates. These results suggest that certain phthalate metabolites may be associated with a known biomarker of systemic oxidative stress. Sperm mitochondrial function as measured by MtCopy and MtDeletion may be considered biomarkers of male infertility, although no relationship was shown between mitochondrial outcomes and oxidative stress. Future research is investigating these relationships with developmental outcomes including embryo quality.

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Dissertations / Theses on the topic 'Isoprostany'

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