Chronic psychological and physiological stress is linked to a high prevalence of cardiovascular disease (CVD). Potentially dangerous cardiovascular responses (e.g., exacerbated cortisol production) can occur with high levels of stress and chronic hypercortisolemia is associated with CVD. The ingestion of carbohydrate (CHO) prior to physical stress may attenuate cortisol responses to stress. The purpose of this project was to investigate the potential effect of CHO ingestion on cortisol production and responses to concurrent stress challenges. Sixteen apparently healthy non-smoking men 21-30 years old participated in a randomized, cross-over, double blind, placebo controlled trial. Participants were tested on four separate sessions. In session 1, general procedures were explained, and participants provided written informed consent as well as a health history questionnaire. Anthropometric data were obtained and participants performed a VO2 peak test during session 2, as well as a 90 sec familiarization session with the mental stress challenges. During the third and fourth sessions, either a 6.6% CHO solution or non-CHO control beverage (water containing non-caloric ingredients tasting like the CHO beverage) was randomly assigned and orally ingested at 0.6g/kg body weight 15 min prior to performing a dual-concurrent-stress (DCS) challenge. The DCS procedure consisted of physical stress (i.e., exercise) combined with computerized mental stress tests of color word associations and arithmetic. Ten mL of blood were obtained at each blood draw: 70, 40, and 15 min prior to the start of exercise, immediately at onset of exercise, 10, 20, 30, and 35 min during exercise, and 15, 30, 45, and 60 min during a post exercise recovery period. There was a significant main effect for treatment regarding mean cortisol production, and the DCS challenge was effective at increasing anxiety and acting as an effective stressor. Mean cortisol production was consistently lower during and after DSC. This is a potential beneficial implication for individuals that work in high-stress conditions. These findings support a prevention based approach to address the high prevalence of CVD among individuals and others working in high-stress occupations such as firefighters.

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<p> This thesis describes the synthesis and characterization of a series of carborane and metallocarborane-carbohydrate conjugates as model systems for developing a novel class of radiophannaceuticals. The role of the carborane group is to provide a site for binding radioactive elements while the carbohydrate moieties are present either as a targeting vector, or as a means by which to increase the hydrophilicity of the overall complex. In this research, the versatility of carboranes was demonstrated since it was shown that carbohydrate-nido-carborane derivatives could be labeled with both metals (Re/99Tc) and halogens (125I/127I). </p> <p> The initial synthetic target was compound 2.6, a simple nido-carboranyl glycoside of glucose. The syntheses of this model ligand and its Re-metallocarborane (2.1, 3.4) and iodinated (2.13) derivatives were carried out in order to determine the optimal methods and conditions for synthesis and purification of bifunctional ligands and the corresponding radioactive analogues. Microwave irradiation was found to greatly enhance the synthesis ofRe and 99mTc-metallocarborane complexes which were isolated in 31% and 58% yield respectively. Analysis of the Re complexes by 1H nOe NMR spectroscopy revealed that rearrangement of the carborane cage from the expected 3,1 ,2- ReC2B9 isomer to the 2,1 ,8- isomer occurred under the synthetic conditions employed. </p> <p> Iodination and radioiodination of model compound 2.6 was carried out using Na[1271] or Na[125I] in the presence of Chloramine-T or Iodogen as oxidants at room temperature. Reactions were complete in 5 min and the products isolated in 21% and 29% yield for 127I and 125I, respectively. </p> <p> Building on these results, bifunctional compounds 4.3 and 4.12 were prepared. Using microwave heating, these compounds were labeled with 99mTc in 62% and 44% yield, respectively. Compounds 4.3 and 4.12 contained a benzoic acid functionality through which conjugation to targeting vectors could be accomplished. To demonstrate this, benzamides 4.14 and 4.16 were synthesized using an active ester approach. The products were isolated in 41% and 35% yield and subsequently labeled with 1251 using the methods developed for the model system. Compounds [1251]-4.23 and [1251]-4.24 were obtained in 73% and 92% yield, respectively. The stability of these [1251]-labeled compounds was excellent, showing less than 1% degradation after 24 hours in solution. In order to assess the effect of the carbohydrate moiety upon lipophilicity, the log P of the radiolabeled benzamides was measured and found to be 1.53±0.01 for [125I]-4.23 and 0.82±0.04 for [1251]-4.24. This result confirmed the increase in hydrophilicity associated with the presence of the carbohydrate moiety. </p> <p> Progress was also made towards preparing a glucose-nido-carborane conjugate (5.9) whose Re and Tc complexes were pursued as metallocarborane analogues of the clinical PET tracer [18F]FDG. The key precursor was made in good overall yield and the product fully characterized. Future work should focus on preparing the radiolabeled analogues. </p> / Thesis / Doctor of Philosophy (PhD)

During the first few hours of recovery from prolonged exercise, co-ingestion of protein (PRO) with carbohydrate (CHO) will increase the rate of muscle glycogen resynthesis if the rate of CHO intake is sub-optimal and/or when the feeding intervals are > 1 h apart (Burke et al.. 2004). It remains controversial whether the higher rate of glycogen resynthesis is attributable to a PRO-mediated increase in insulin release or simply the result of higher energy intake (Jentjens et al., 2001). The optimal rate of CHO ingestion necessary to maximize glycogen resynthesis remains unknown, although some studies have recommended a peak CHO intake of >1.2 g/kg/h. PURPOSE: We examined whether the addition of PRO or “extra CHO” to a drink that provided 1.2 g CHO/kg/h would increase muscle glycogen resynthesis during recovery from prolonged exercise. METHODS: Six men (22± 1 yr; V02|,eilk= 48±8 ml/kg/min) were studied during a 4-h recovery period on 3 separate occasions after a standardized 2-h exercise protocol designed to substantially lower muscle glycogen. Subjects randomly consumed 1 of 3 drinks during recovery from each trial: 1.2 gCHO/kg/h (CHO), 1.6 gCHO/kg/h (CHO/CHO) or 1.2 gCHO + 0.4 gPRO/kg/h (CHO/PRO). Drinks were consumed immediately post-exercise and at 15 min intervals for 3 hrs. RESULTS: Biopsies obtained at 0 and 4 hrs post-exercise revealed no difference in muscle glycogen resynthesis rates between trials (CHO: 22.7±6.6; CHO/CHO: 25.0±3.0; CHO/PRO: 24.6±4.2 mmol/kg dry wt/h) despite differences in energy intake between trials. The ingestion of additional CHO or PRO did not induce changes in blood [insulin ] and blood [glucose] compared to a 1.2 gCHO/kg/h beverage. Muscle [lactate] increased from immediately post-exercise to 4 hrs into recovery in all 3 trials (main effect for time. P<0.05). All subjects reported some degree of gastro-intestinal(Gl) distress after 3 and 4 hrs of recovery but there were no differences between treatments (main effect for time, P<0.05 vs. 0 hrs). CONCLUSION: Ingesting 1.2 gCHO/kg/h met or exceeded the threshold necessary to optimize muscle glycogen synthesis during the first 4 hrs of recovery from prolonged, strenuous exercise in recreationally active men. The ingestion of >1.2 gCHO/kg/h at a concentration of -20% solution induced GI distress in some individuals and may hamper subsequent same-day performance. / Thesis / Master of Science (MS)

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Two recent studies (Ivy et al., Int J Sports Nutr Exerc Metab 13:382-395, 2003; Saunders et al., Med Sci Sports Exerc 36:1233-1238, 2004) reported dramatic (>25%) increases in endurance time to fatigue during cycling at 75-85% V0₂peak when subjects ingested a ~2% protein (PRO) plus ~7% carbohydrate (CHO) drink as compared to CHO alone. However, the research designs employed in these studies have been criticized for several reasons, including (1) the rate of CHO and fluid provided was less than what is considered optimal for endurance performance (i.e., 6% CHO, ingested at a rate of 15 g in 250 ml of fluid, every 15 min); and (2) the nature of the performance tests did not mimic the way in which athletes typically compete (i.e., a race, in which a given distance must be covered as quickly as possible). Purpose: To determine whether the addition of 2% Pro to a 6% CHO drink (CHO-Pro) improves 80 km cycling time trial performance as compared to a 6% CHO drink and a non-energetic sweetened placebo. Methods: Ten well-trained cyclists (25±5 y; V0₂peak = 63±5 ml/kg/min; means±SD) completed a simulated 80 km time trial (TT) on three separate occasions separated by 5-7 d. In a randomized, double-blind manner, subjects ingested either CHO-Pro, CHO or placebo at a rate of 250 ml every 15 min. All trials were performed on a Computrainer (RacerMate, Seattle, WA) using each subject's own bicycle with no temporal, verbal or physiological feedback. Venous blood samples were obtained periodically during exercise and subsequently analyzed for glucose, lactate, free fatty acids, ammonia and insulin concentrations. Results: Analysis of variance revealed that time to complete the 80 km TT was lower (P≤0.05) when subjects ingested CHO (135±9 min; mean±SD) and CHOPro (135±9) compared to placebo (141±10), with no difference between CHO-Pro and CHO. Average power output was higher (P<0.05) when subjects ingested CHO and CHO-Pro versus placebo, and work intensity averaged 81±1%, 80±1% and 78±1% of heart rate reserve for the CHO, CHO-Pro and placebo rides, respectively. Improved performance of the two CHO trials was primarily attributed to maintenance of blood glucose concentration during the later stages of exercise. Conclusion: Ingestion of a 6% CHO drink at a rate of 1 L/h improves 80 km TT performance, as compared to a non-energetic placebo, in trained male cyclists. However, the addition of 2% Pro to a 6% CHO drink provides no additional performance benefit. / Thesis / Master of Science (MSc)

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2 pp. / discontinued 3/4/11 / Food intake tips for training and competition.

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