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Sperm Mitochondrial Copy Number and Associations with Oxidative Stress and Phthalate Metabolites in Male Partners Undergoing Assisted Reproductive TechnologiesOlmsted, Alexandra 11 July 2017 (has links)
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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The impact of lifestyle, age, and sex on systemic and airway inflammation and oxidative stressKurti, Stephanie P. January 1900 (has links)
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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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 / Nutritional status of zinc in patients with rheumatoid arthritis and its relationship with oxidative stress and Arg213Gli polymorphism in the superoxide dismutase 3 gene.Silva, Graziela Biude 04 December 2013 (has links)
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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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 / Nutritional status of zinc in patients with rheumatoid arthritis and its relationship with oxidative stress and Arg213Gli polymorphism in the superoxide dismutase 3 gene.Graziela Biude Silva 04 December 2013 (has links)
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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Determination of biomarkers for lipid peroxidation and oxidative stress : Development of analytical techniques and methodsClaeson Bohnstedt, Kristina January 2005 (has links)
<p>Oxidative stress can be defined as a state of disturbance in the pro-oxidant/antioxidant balance in favour of the former, leading to potential damage. Processes associated with oxidative stress involve reactive oxygen species and radicals and can result in elevated levels of oxidatively modified or toxic molecules that can cause cellular malfunction, and even cell death. Destruction of membrane lipids, lipid peroxidation, caused by reactive oxygen species and radicals has been coupled to many diseases and also normal ageing. </p><p>The measurement of low molecular weight biomarkers of oxidative stress present in complex matrices such as brain tissue, plasma, urine or cerebrospinal fluid is a delicate and difficult task and there is a need for improved analytical tools in this field of research. </p><p>The major foci of this thesis and the work underlying it are the development of analytical techniques and methods for determining biomarkers for oxidative stress and lipid peroxidation. Aspects of particular concern include the effects of sample treatments prior to analysis, evaluation of the developed methods with respect to possible artefacts, and the scope for results to be misinterpreted. The specific research goals and issues addressed are detailed in five papers, which this thesis is based upon.</p><p><b>Paper I</b> focuses on malondialdehyde, describing and evaluating two new simplified sample pre-treatment regimes for the determination of malondialdehyde in rat brain tissue by capillary electrophoresis with UV detection. The effects of sample storing and handling are also considered.</p><p><b>Paper II</b> describes the synthesis, characterization and implementation of a new internal standard for the determination of malondialdehyde in biological samples using electrophoretic or chromatographic separation techniques. The usefulness of the internal standard is demonstrated in analyses of rat brain tissue samples.</p><p><b>Paper III</b> presents a method for the determination of 4-hydroxynon-2-enal in brain tissue from rats employing micellar electrokinetic chromatography separation and laser-induced fluorescence detection. </p><p><b>Paper IV</b> is focused on the development of a new methodology for determining the stereoisomeric F2-isoprostanes in human urine samples employing chromatographic separation on porous graphitic carbon and detection by electrospray ionization-tandem mass spectrometry. The results from this study conflict with the hypothesis that peripheral isoprostanes are elevated in patients with Alzheimer’s disease.</p><p><b>Paper V</b> describes porous graphitic carbon chromatography-tandem mass spectrometry for the determination of isoprostanes in human cerebrospinal fluid. A new simplified sample pre-treatment regime, involving a column switching technique, is presented that allows direct injection of a relatively large volume of CSF into the chromatographic system.</p>
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Experimental cardiopulmonary cerebral resuscitation : A study of cerebral perfusion with special reference to the postresuscitation disturbancesNozari, Ala January 2000 (has links)
<p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>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 <i>during</i> CPR, whereas a significant increase was recorded <i>after</i> 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.</p><p>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<sub>2α</sub>, a major isoprostane and a novel index of oxidative injury. 8-iso-PGF<sub>2α</sub>, and the prostaglandin 15-K-DH-PGF<sub>2α</sub>, 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.</p>
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Experimental cardiopulmonary cerebral resuscitation : A study of cerebral perfusion with special reference to the postresuscitation disturbancesNozari, Ala January 2000 (has links)
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-PGF2α, a major isoprostane and a novel index of oxidative injury. 8-iso-PGF2α, and the prostaglandin 15-K-DH-PGF2α, 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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Determination of biomarkers for lipid peroxidation and oxidative stress : Development of analytical techniques and methodsClaeson Bohnstedt, Kristina January 2005 (has links)
Oxidative stress can be defined as a state of disturbance in the pro-oxidant/antioxidant balance in favour of the former, leading to potential damage. Processes associated with oxidative stress involve reactive oxygen species and radicals and can result in elevated levels of oxidatively modified or toxic molecules that can cause cellular malfunction, and even cell death. Destruction of membrane lipids, lipid peroxidation, caused by reactive oxygen species and radicals has been coupled to many diseases and also normal ageing. The measurement of low molecular weight biomarkers of oxidative stress present in complex matrices such as brain tissue, plasma, urine or cerebrospinal fluid is a delicate and difficult task and there is a need for improved analytical tools in this field of research. The major foci of this thesis and the work underlying it are the development of analytical techniques and methods for determining biomarkers for oxidative stress and lipid peroxidation. Aspects of particular concern include the effects of sample treatments prior to analysis, evaluation of the developed methods with respect to possible artefacts, and the scope for results to be misinterpreted. The specific research goals and issues addressed are detailed in five papers, which this thesis is based upon. <b>Paper I</b> focuses on malondialdehyde, describing and evaluating two new simplified sample pre-treatment regimes for the determination of malondialdehyde in rat brain tissue by capillary electrophoresis with UV detection. The effects of sample storing and handling are also considered. <b>Paper II</b> describes the synthesis, characterization and implementation of a new internal standard for the determination of malondialdehyde in biological samples using electrophoretic or chromatographic separation techniques. The usefulness of the internal standard is demonstrated in analyses of rat brain tissue samples. <b>Paper III</b> presents a method for the determination of 4-hydroxynon-2-enal in brain tissue from rats employing micellar electrokinetic chromatography separation and laser-induced fluorescence detection. <b>Paper IV</b> is focused on the development of a new methodology for determining the stereoisomeric F2-isoprostanes in human urine samples employing chromatographic separation on porous graphitic carbon and detection by electrospray ionization-tandem mass spectrometry. The results from this study conflict with the hypothesis that peripheral isoprostanes are elevated in patients with Alzheimer’s disease. <b>Paper V</b> describes porous graphitic carbon chromatography-tandem mass spectrometry for the determination of isoprostanes in human cerebrospinal fluid. A new simplified sample pre-treatment regime, involving a column switching technique, is presented that allows direct injection of a relatively large volume of CSF into the chromatographic system.
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Biomarkers of oxidative stress and inflammation in biological samples collected from recurrent airway obstruction (RAO)-affected horses and their controlsTan, Rachel Hsing Hsing 10 June 2008 (has links)
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 (INFγ), 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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Exposição aguda ao material particulado total em suspensão proveniente de diferentes fontes e suas repercussões nas respostas inflamatórias, sistêmica e local, em ratos / Acute exposure to total suspended particles from different sources and their impacts on both systemic and local inflammatory responses in ratsColombini, Marjorie Paris 21 September 2007 (has links)
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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