No description available.

No description available.

Supraphysiologic concentrations of oxygen are used in the management of critically ill patients across the lifespan. However, hyperoxia (HO) results in alveolar- capillary membrane destruction, pulmonary edema, pleural effusions, infiltration and activation of inflammatory cells, altered pulmonary mechanics and gas exchange prompting increased loading of the respiratory muscle. These abnormalities of pulmonary structure and function increase the work of breathing necessitating increased respiratory muscle force production to maintain alveolar ventilation. When the load placed on the respiratory muscle pump exceeds its capacity, respiratory failure develops and is ultimately fatal unless therapeutic interventions are able to reduce the ventilatory load. The use of perfluorochemical (PFC) liquids as a respiratory medium has been effective in the treatment of respiratory distress syndrome and acute lung injury (ALI) requiring mechanical ventilation. Mechanistically, by eliminating the air-liquid interface, PFC liquids reduce surface tension enabling lung volume recruitment at low inspiratory pressures and have high respiratory gas solubility which supports gas exchange. Additionally, through mechanical as well as cytoprotective mechanisms, intrapulmonary PFC liquids reduce inflammatory cell activation and recruitment. Cell culture, animal and human studies have suggested that acute and chronic lung injury secondary to prolonged HO may be ameliorated by administration of antioxidant enzymes (AOE), with superoxide dismutases (SOD) having significant protective effects. Because the lung is exposed to the highest O2 concentrations, a logical strategy to reduce HO-induced damage is to specifically target antioxidant enzymes to the lungs. However, intratracheal delivery of AOE by vehicles like normal saline may transiently impair lung function and be poorly distributed. PFC fluids have previously been shown to be effective respiratory media for pulmonary administration of various drugs. The premise of the proposed studies are to to characterize hyperoxic lung injury in a spontaneously breathing animal model and to develop therapeutic strategies to reduce oxidatative stress and supplement endogenous AOE. With respect to the diaphragm, we reason that HO-induced lung damage and oxidative stress will increase contractile demand of the diaphragm. If AOE activity could be increased in the lungs and respiratory muscles with AOE proteins or the genes encoding these enzymes, then cell damage, inflammatory changes, damage to the lung and respiratory "pump" might be ameliorated or prevented. The results show that PFC and SOD can attenuate the HO- induced decline in lung mechanics and gas exchange, ameliorate the inflammatory and oxidative stress profiles, and promote lung and muscle structural integrity resulting in a survival benefit. These findings support the novel application of PFC liquids in a spontaneously breathing model and support the concept that PFC preconditioning and AOE supplementation play a protective role by reducing mortality and morbidity in hyperoxic lung injury. / Physiology

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No description available.

No description available.

Master of Science / Department of Kinesiology / Thomas J. Barstow / Background and Aim: Long-term microgravity exposure, via spaceflight or -6° head-down tilt bedrest, has been shown to produce significant cardiovascular deconditioning and decreases in exercise performance. However, there is little known about how acute microgravity exposure influences the cardiovascular system’s ability to adjust to increases in physical work. Therefore, the aim of this study was to compare cardiovascular and exercise performance during acute upright, supine and -6° head-down tilt positions. Methods: Seven healthy inactive men performed maximal cycle exercise (VO2peak) tests in the upright, supine, and -6° head-down tilt on separate days. Oxygen consumption and heart rate were measured continuously throughout the testing procedures. Cardiac output (acetylene exhalation technique) was measured periodically and interpolated to the 100-watt work rate. Stroke volume was calculated from cardiac output and heart rate data. Results: Peak oxygen uptake and heart rate were significantly decreased in the supine and -6° head-down tilt positions compared to the upright (VO2peak 2.01±0.46, 2.01±0.51 versus 2.32±0.61 L/min respectively; peak heart rate 161±13, 160±14 versus 172±11 bmp). However, cardiac output at 100-watts was similar in all three-exercise positions. Calculated stroke volume at 100-watts was significantly higher in the -6° head-down tilt position compared to the upright position (76.6±4.7 versus 71.2±4.5, ml). Conclusion: These results suggest that exercise capacity is immediately decreased upon exposure to a microgravity environment, prior to any cardiovascular deconditioning. Therefore, an astronaut’s exercise performance should be evaluated with exercise tests in the -6° head-down tilt position prior to space flight in order to establish a baseline response.

Master of Science / Department of Anatomy and Physiology / Deryl L. Troyer / There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands. The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. There is a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure. These results indicate that intratumoral administration of surface-modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, intravenous administration of these MNPs followed by AMF exposure attenuates melanomas, indicating that adequate amounts of TCPP-labeled stealth Fe/Fe3O4 nanoparticles can accumulate in murine melanoma after systemic delivery to allow effective magnetic hyperthermic therapy in a rodent tumor mode.

The purpose of this study was to revise and expand the Hope Maintenance Scale. An exploratory design was used to content analyze qualitative data collected from 226 heart transplant patients in the primary study, "Predictors of Quality of Life in Heart Transplantation". Results supported five of the six original dimensions of hope contained in the Hope Maintenance Scale. The five dimensions substantiated were: Downward Comparison, Fostering Optimism, Belief in a Powerful Other, Avoiding Painful Situations or Material, and Viewing the Situation as Temporary. Subcategories for the dimension of Optimism were generated and termed: Forced Optimism, Guarded Optimism, Euphoria, and Gratefulness. The subcategory of Exceptional Experience was developed for the category of Downward Comparison. Normalizing was proposed as an antecedent of hope. Of subjects who expressed normalizing activities, 60% also used other hope maintenance strategies. Of subjects who reported Threats to Normalizing, 42% used no other hope maintenance strategies.

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