Cardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of this study is to understand the modulation of key molecular mechanisms involving stress proteins and VEGF that offer neuroprotection and enhance cell survival in the freshwater turtle through anoxia and reoxygenation. In vivo analyses have shown that anoxia induced stress proteins (Hsp72, Hsp60, Grp94, Hsp60, Hsp27, HO-1); modest changes in the Bcl2/Bax ratio and no change in cleaved caspase-3 expression suggesting resistance to neuronal damage. These results were corroborated with immunohistochemical evidence indicating no damage in turtle brain when subjected to the stress of anoxia and A/R. To understand the functional role of Hsp72, siRNA against Hsp72 was utilized to knockdown Hsp72 in vitro (neuronally enriched primary cell cultures established from the turtle). Knockdown cultures were characterized by increased cell death associated with elevated ROS levels. Silencing of Hsp72 knocks down the expression of Bcl2 and increases the expression of Bax, thereby decreasing the Bcl2/Bax ratio. However, there was no increase in cytosolic Cytochrome c or the expression levels of cleaved Caspase-3. Significant increase in AIF was observed in the knockdown cultures that increase through anoxia and reoxygenation, suggesting a caspase independent pathway of cell death. / Expression of the master regulator of hypoxia, HIF1 alpha and its target gene, VEGF, were analyzed at the mRNA and protein levels. The results showed no significant increase in HIF-1 alpha levels but anoxia VE GF The levels of stress proteins and VEGF returned to control levels during reoxygenation suggesting robust ROS protection mechanisms through reoxygenation. The present study thereby emphasizes Trachemys scripta as an advantageous model to examine anoxia and reoxygenation survival without major damage to the brain due to it's modulation of molecular mechanisms. / by Shailaja Kesaraju. / Thesis (Ph.D.)--Florida Atlantic University, 2008 / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

Qian, Wei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 184-199). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Embryos of the annual killifish Austrofundulus limnaeus display a remarkable tolerance to anoxia during development, most notably during embryonic diapause. Little is known about the metabolic or enzymatic changes that accompany this state of anoxia tolerance. This study examined the metabolic changes associated with exposure to anoxia by measuring the activity of the enzyme phosphoenolpyruvate carboxykinase (PEPCK), and by profiling the concentration of 31 metabolites ranging from amino acids to citric cycle intermediates at 4 different developmental stages, diapause 2 (DII), 4 days post diapause (dpd), 12 and 22 dpd. Embryos of A. limnaeus showed stage specific changes in concentrations of several metabolites. The most notable changes in metabolite concentration in response to anoxia were the increases of lactate, alanine, GABA and succinate as well as a pronounced decrease in aspartate concentrations. However, a complete understanding of the mechanisms by which anoxia tolerance is achieved remains elusive. Further studies into the tissue specific responses of anoxia would enable greater resolution when attempting to explain changes in concentrations of metabolites both during development and in response to anoxic insult.

Bibliography: leaves 144-163 / xi, 163 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, 1985

published_or_final_version / abstract / toc / Medicine / Master / Master of Philosophy

No abstract available.

Weight loss is a common occurrence in patients with human immunodeficiency virus (HIV) and contributes to further debilitation in the acquired immune deficiency syndrome (AIDS). Wasting syndrome (WS) is defined as 10% or more unintentional weight loss from usual body weight. The etiology of WS includes alterations in metabolism, which contribute to loss of lean body mass. Cytokine driven oxidative stress may play a critical role in the metabolic pathways that lead to HIV wasting. Studies have shown that that patients infected with HIV may have a depleted antioxidant (AO) defense system, the integrity of which is needed to efficiently scavenge reactive oxygen species (ROS). It has been theorised that low AO intake may contribute to a depressed AO defense system, which drives oxidative stress (OS). In this study we examined 16 subjects who had documented WS but no active infectious process, stratified into 10 to 15% weight loss (n = 7) and over 15% weight loss (n = 9) groups, and reported on oxidative stress measures and AO intake. (Abstract shortened by UMI.)

'The rate of living' hypothesis of aging speculates that the metabolic rate of a species ultimately determines its life expectancy. Using the nematode worm Caenorhabditis elegans as model system, mutation in twp-1 (t&barbelow;ime w&barbelow;arp) gene was found to significantly delay biological timing and remarkably increase mean and maximum life span. The rate of living in twp-1 is dramatically delayed in all the biological processes we tested, including rates of rhythmic adult behaviors, development, and reproduction. Oxygen consumption, which indicates metabolic rate of an organism, is reduced to approximately two-fold in twp-1 mutant. According to my study, twp-1 and dauer genes, daf-2 and daf-16, interact to determine biological timing and adult life span. twp-1 mutation prolongs life span in a way that is at least partially different from dauer formation mutants, whose longevity might due to their high resistance to stresses, especially oxidative stress. twp-1 gene is cloned and found to encode iron-sulfur protein (ISP) in complex III, which is the major site of mitochondrial superoxide radical production, of the mitochondrial respiratory chain. This suggests that twp-1 may live long because they produce less reactive oxygen species (ROS), and thus, result in less oxidative damage. mts-1 (mitochondrial twp-1 suppressor) mutation can fully or partially rescue most of the biological timing in twp-1 mutant, including both developmental and behavioral rates, but except life span. mts-1 encodes another subunit of complex III, cytochrome b, which normally interact with ISP during function. mts-1 might somehow restore the activity of complex III, and consequently, accelerate the rate of living. Paraquat, a herbicide that induces the formation of superoxide, was used to provide an acute oxidative stress to animals. twp-1; mts-1 was found to be highly resistant to paraquat, indicating that twp-1 animals are well capable of coping with oxidative stress. According to o

This study examined the influence of maturation on the oxygen uptake efficiency slope (OUES) in healthy male subjects. The variables comprising the OUES are known to be affected by metabolism which in turn is influenced by maturation. The subjects performed a graded exercise test on a cycle ergometer to determine the OUES and VO2max. Subjects were divided into groups based on maturation status: early-pubertal (EP, n = 15), mid-pubertal (MP, n = 20), late-pubertal (LP, n = 17), and young-adult (YA, n = 19) males. Cardiorespiratory fitness (measured as VO2max mL·min-1·kg-1) was not significantly different between groups. OUES values in absolute terms were higher in groups LP and YA versus MP and EP. Scaling OUES relative to body mass failed to eliminate between group differences whereby LP and YA had lower mass relative OUES values compared to LP and YA. Scaling OUES relative to fat free mass also failed to eliminate between group differences with EP group values being higher versus LP and YA, but only MP values being higher than YA. Differences in OUES values between male across maturation status remained after accounting for differences in body size, suggesting an affect of maturation on this measurement. / School of Physical Education, Sport, and Exercise Science

Bibliography: leaves 144-163 / xi, 163 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, 1985