Thesis (M.S.)--University of Central Florida, 2008. / Adviser: Michael Dunn. Includes bibliographical references (p. 50-57).

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2007. / Committee Chair: Sheldon W. May ; Committee Members: Donald F. Doyle, Leslie T. Gelbaum, Stanley H. Pollock, and James Powers. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Th.--Sci. phys.--Besançon, 1977. N°: 120.

Introduction: Exposure to hypoxia may alter substrate utilization through diverse mechanisms. Acute hypoxia is known to increase circulating nonesterified fatty acid (NEFA) levels and reduce systemic sensitivity to insulin. The hepatic fate of NEFA is dictated by major pathways such as esterification to triglycerides and complete/partial oxidation, the latter leading to ketogenesis. To our knowledge, the effect of hypoxia on ketogenesis, more specifically ß-hydroxybutyrate (ßOHB), remains unknown in humans. Moreover, adipose tissue is a significant site of NEFA liberation into circulation, and insulin inhibits this process. Under acute hypoxia, systemic insulin resistance develops, and the suppression of lipolysis is impeded. Therefore, the objective of this study was to determine the effect of acute hypoxia on plasma circulating ßOHB levels. Furthermore, to better understand how hypoxic and prandial conditions may modulate plasma NEFA and ketonemia, we calculated the βOHB:NEFA ratio and the adipose tissue insulin resistance index (Adipo-IR), which respectively gives indications of the partial hepatic oxidation of NEFA and the adipose tissue insulin sensitivity. Methods: Plasma samples from 3 different randomized crossover studies were retrospectively assessed for ßOHB concentrations. In the first study, 14 healthy men (23 ± 3.5 years) were exposed to 6 hours of normoxia or intermittent hypoxia (IH) (15 hypoxic events per hour) following an isocaloric meal (IH-Fed). In the second study, 10 healthy men (26 ± 5.6 years) were exposed to 6 hours of continuous normobaric hypoxia (CH) (FiO2= 0.12) or normoxic conditions in the fasting state (CH-Fasted). In the third study, 9 healthy men (24 ± 4.5 years) were exposed to 6 hours of CH in a constant prandial state. ßOHB, NEFA and insulin levels were measured during all sessions (CH-Fed). The adipose tissue insulin resistance index (Adipo-IR) was also calculated from NEFA and insulin levels. Results: In study 1 (IH-Fed), ßOHB and NEFA levels tended to be greater over 6 hours of IH (condition x time interaction, p = 0.108 and p = 0.062, respectively) compared to normoxia. In study 2 (CH-Fasted), ßOHB and NEFA levels increased over time in both experimental conditions, and this effect tended to be greater under CH (condition x time interaction, p = 0.070 and p = 0.046, respectively). In study 3 (CH-Fed), ßOHB levels slightly increased up to 180 min before falling back to initial concentrations by the end of the protocol in both normoxia and CH (p = 0.062), while NEFA slightly increased under CH (p = 0.006). Adipo-IR tended to increase after 6 hours of hypoxia compared to normoxia in the first two studies (main effect of condition, p = 0.024; p = 0.097, respectively), and significantly increased over time under hypoxia in CH-Fed (condition x time interaction, p = 0.004). Conclusion: Acute normobaric hypoxia exposure significantly increases plasma ßOHB concentrations over time in healthy men. The stimulating effect of hypoxia on plasma ßOHB levels is however attenuated during postprandial and postprandial states. Contribution to advancement of knowledge: To our knowledge, this research provides some of the first evidence that an acute exposure to hypoxia increases plasma ßOHB levels in humans. It also reveals potential underlying mechanism that modulate ketogenesis upon hypoxia exposure. Overall, this thesis provides further insights into the homeostatic response of healthy men to oxygen deprivation.

This diploma thesis deals with the characterization of rheological properties and biodegradation of a poly(3-hydroxy-co-4-hydroxybutyrate), a copolymer produced by a strain of Cupriavidus malaysiensis. The theoretical part focuses on the rheology and degradation of polymers in general. It also contains the basic characteristics of polyhydroxyalkanoates and deals in more details with the description of the studied copolymer, its properties, synthesis, decomposition and possibilities of its applications. In the experimental part, the given copolymer was investigated in its native form and also in the form of copolymer mixtures filaments, which were enriched with additives (stabilizers and plasticizers). In terms of rheology, the samples showed pseudoplastic behaviour, which was slightly limited by the plasticization of the material. The highest thermal stability observed as a function of changes in complex viscosity over time was observed in a sample of a copolymer mixture containing stabilizers and plasticizer Citrofol BII. The plasticization also caused significant changes in thermal properties, especially crystallinity, which decreased compared to the native copolymer. In vitro degradation studies of samples in the form of films prepared by dissolving copolymer mixtures in chloroform were performed in phosphate buffer with lipase, in simulated body fluid and in synthetic gastric juice. The course of the process itself was characterized by the method of determining the molecular weight (SEC-MALLS) and the weight loss over time (gravimetrically). The results showed that the analysed samples are subject to degradation in all used environments. The most considerable molecular weight loss after 105 days (76 %) was observed in the sample containing stabilizers and plasticizer Citrofol BII in the environment of synthetic gastric juice. The most extensive gravimetric weight loss was attributed to the sample with stabilizers and without plasticizers, in the environment of phosphate buffer with lipase, specifically by 79%.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1994. / Vita. Abstract. Includes bibliographical references (leaves 136-141). Also available via the Internet.

Thesis (Ph. D.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains xi, 130 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 127-130).

Thesis (Ph.D.)--Baylor University, 2006. / Includes bibliographic references (p. 163-189).

There has been much consideration over whether exogenous ketone bodies have the capacity to enhance exercise performance through altered substrate metabolism. This systematic review aimed to determine the effects of both ketone precursors and monoesters on endurance exercise performance. A systematic search was conducted in PubMed, SPORTDiscus, and CINAHL for randomized controlled trials investigating endurance performance outcomes in response to ingestion of a ketone supplement compared to a nutritive or non-nutritive control in humans. A meta-analysis was performed to determine the standardized mean difference between interventions using a random-effects model. Hedges’ g and 95% confidence intervals (CI) were reported. The search yielded 569 articles, of which 8 were included in this review (80 participants; 77 men, 3 women). When comparing endurance performance amongst all studies, no significant differences were found between ketone and control trials (Hedges g=0.136; 95% CI, -0.195, 0.467; p=0.419). Sub-analyses based on type of endurance tests showed no significant differences in time to exhaustion (Hedges g=-0.002; 95% CI, -0.312, 0.308; p=0.989) or time trial (Hedges g=0.057; 95% CI, -0.282, 0.395; p=0.744) values. Based on these findings, exogenous ketone precursors and monoesters do not significantly improve endurance exercise performance. While all studies reported an increase in blood ketone concentrations after ingestion, ketone monoesters appear to be more effective at raising concentrations than precursors.

Legionella pneumophila, the causative agent of Legionnaires’ disease (LD), is an intracellular pathogen of freshwater protozoa that can also persist in the environment as a free-living bacterium. L. pneumophila has many morphological forms that fit within a developmental cycle. In water, L. pneumophila enters into a viable but non-culturable (VBNC) state that is largely uncharacterized. VBNC cells were produced from two developmental L. pneumophila forms, stationary phase forms (SPFs) and mature infectious forms (MIFs) by suspension in double deionized (dd) or tap-water at 45°C. Electron microscopy results showed that VBNC cells have a unique morphology and that in tap water they lose their poly 3-hydroxybutyrate inclusion bodies. Both SPFs and MIFs lost culturability faster in dd- than in tap water, and addition of salts to dd-water prolonged L. pneumophila culturability and enhanced viability. However, MIFs retained higher viability in dd- and tap water (85% and 51%, respectively) than SPFs (5% and 20%, respectively) as determined by the BacLight vital stain. Only ~1 VBNC cell out of 105 of those produced from SPFs in tap water regained culturability via infection of Acanthamoeba. All VBNC cells, except for those produced from SPFs in dd-water, resisted both digestion inside Tetrahymena spp. and detergent-mediated lysis. SDS-PAGE analysis and shotgun proteomics revealed a number of VBNC cell specific proteins; one of these was 3-hydroxybutyrate dehydrogenase (BdhA), which is involved in the metabolism of poly 3-hydroxybutyrate inclusion bodies. A bdhA mutant showed an early loss of culturability and a dramatic decrease in viability as compared to the parent strain, and complementing the mutant with a functional bdhA gene restored the parent's strain phenotypes. In conclusion, VBNC L. pneumophila has a distinct morphology and physiology that varies according to the developmental stage and the environmental conditions used to produce such VBNC cells. VBNC cells have a different protein profile and morphology than the culturable cells, suggesting that this state constitutes a distinct differentiated form within the developmental cycle of L. pneumophila. BdhA seems to influence L. pneumophila survival and hence VBNC cell formation. Collectively, the results from this study provide a better understanding of L. pneumophila VBNC form and the factors influencing its formation.