"May 2002." / Bibliography: leaves 123-144. / xiv, 144 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aspects of the control of ventilation and an upper airway dilator muscle (genioglossus) are compared between healthy men and women, in an attempt to identify a gender difference that may contribute to the high male prevalence of sleep apnea. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2002

[Truncated abstract] This thesis describes the development, clinical validation and initial application of a technique for taking measurements of the shape and dimensions of the human upper airway, called anatomical optical coherence tomography (aOCT). The technique uses a transparent catheter containing a rotating optical probe which is introduced transnasally and positioned in the airway and oesophagus. Optical coherence tomography is used to take calibrated cross-sectional images of the airway lumen as the probe rotates. The probe can also be advanced or withdrawn within the catheter during scanning to build up three-dimensional information. The catheter remains stationary so that the subject is not aware of the probe motion. The initial application of the system is research into obstructive sleep apnoea (OSA), a serious condition characterized by repetitive collapse of the upper airway during sleep and an independent risk factor for deaths by heart disease, strokes or car accidents. Measurement of upper airway size and shape is important for the investigation of the pathophysiology of OSA, and for the development and assesment of new treatments. . . We have used aOCT to capture three-dimensional data sets of the airway shape from upper oesophagus to the nasal cavity, undertaken measurements of compliance and other airway characteristics, and recorded dynamic airway shape during confirmed sleep apnoea events in a hospital sleep laboratory. We have shown that aOCT generates quantitative, real-time measurements of upper airway size and shape, allowing study over lengthy periods during both sleep and wakefulness. These features should make it useful for study of upper airway behavior to investigate OSA pathophysiology, and aid clinical management and treatment development.

Bag-valve mask (BVM) ventilation maintains a patient's oxygenation and ventilation until a more definitive artificial airway can be established. In the prehospital setting of a traffic collision or medical aid scene this is performed by an Emerency Medical Technician or medical first responder. Few studies have looked at the effectiveness of Bag-valve masks (BVM) or the complication rate of ventilating an unprotected airway. The purpose and goal of this study is to educate both medical first responders and basic emergency medical technicians.

The allergic disease of asthma is characterized by an infiltration of inflammatory cells to the lung, a process co-ordinated by T-helper (TH) cells. The TH2 cytokine Interleukin (IL)-4 promotes infiltration of eosinophils to sites of inflammation. Eosinophil-selective chemoattractant cytokines (eg. eotaxins) are synthesized by lung epithelial cells. Eotaxin-3 is expressed at high levels in the asthmatic lung, predominantly after IL-4 stimulation. Eotaxin-3 is therefore a marker of inappropriate airway inflammation. Polyphenolic (PP) compounds found in high concentrations in berries may have beneficial effects in inflammatory conditions. Plant and Food Research produced high-PP extracts of blackcurrant (BC) cultivars that were tested for inflammation modulating effects. Since high doses of PPs have been shown to cause cell death, we tested two BC cultivars at a range of concentrations in a cell viability (WST-1) assay. While no toxic effects were attributable to the BC extracts (1-50µg/ml), a dose-related trend in cell death was observed and therefore 10µg/ml was chosen for further experiments Ten BC cultivars were compared for efficacy by measuring eotaxin-3 production in IL-4 stimulated human lung epithelial (A549) cells in vitro. Cells were incubated with BC extracts (10µg/ml) and IL-4 (10ng/ml) for 24 hours. The supernatants were then quantified for eotaxin-3 levels by an enzyme-linked immunosorbent assay (ELISA). All ten BC extracts reduced eotaxin-3 levels after stimulation with IL-4, and six BC extracts were effective by statistically significant levels (P<0.05), (BC cultivars -01, -02, -03, -05, -09 & -10). Of those, BC extracts of four cultivars demonstrated a reduction of more than 65% from the IL-4 stimulated control. In addition, a positive trend in inflammation modulation vs. one anthocyanin (ACN) in the BC extracts was shown. This study has demonstrated the beneficial inflammation modulatory effects of polyphenolic BC extracts, which could be related to cyanidin 3-O-rutinoside content. These results may have therapeutic potential for asthma.

The allergic disease of asthma is characterized by an infiltration of inflammatory cells to the lung, a process co-ordinated by T-helper (TH) cells. The TH2 cytokine Interleukin (IL)-4 promotes infiltration of eosinophils to sites of inflammation. Eosinophil-selective chemoattractant cytokines (eg. eotaxins) are synthesized by lung epithelial cells. Eotaxin-3 is expressed at high levels in the asthmatic lung, predominantly after IL-4 stimulation. Eotaxin-3 is therefore a marker of inappropriate airway inflammation. Polyphenolic (PP) compounds found in high concentrations in berries may have beneficial effects in inflammatory conditions. Plant and Food Research produced high-PP extracts of blackcurrant (BC) cultivars that were tested for inflammation modulating effects. Since high doses of PPs have been shown to cause cell death, we tested two BC cultivars at a range of concentrations in a cell viability (WST-1) assay. While no toxic effects were attributable to the BC extracts (1-50µg/ml), a dose-related trend in cell death was observed and therefore 10µg/ml was chosen for further experiments Ten BC cultivars were compared for efficacy by measuring eotaxin-3 production in IL-4 stimulated human lung epithelial (A549) cells in vitro. Cells were incubated with BC extracts (10µg/ml) and IL-4 (10ng/ml) for 24 hours. The supernatants were then quantified for eotaxin-3 levels by an enzyme-linked immunosorbent assay (ELISA). All ten BC extracts reduced eotaxin-3 levels after stimulation with IL-4, and six BC extracts were effective by statistically significant levels (P<0.05), (BC cultivars -01, -02, -03, -05, -09 & -10). Of those, BC extracts of four cultivars demonstrated a reduction of more than 65% from the IL-4 stimulated control. In addition, a positive trend in inflammation modulation vs. one anthocyanin (ACN) in the BC extracts was shown. This study has demonstrated the beneficial inflammation modulatory effects of polyphenolic BC extracts, which could be related to cyanidin 3-O-rutinoside content. These results may have therapeutic potential for asthma.

The allergic disease of asthma is characterized by an infiltration of inflammatory cells to the lung, a process co-ordinated by T-helper (TH) cells. The TH2 cytokine Interleukin (IL)-4 promotes infiltration of eosinophils to sites of inflammation. Eosinophil-selective chemoattractant cytokines (eg. eotaxins) are synthesized by lung epithelial cells. Eotaxin-3 is expressed at high levels in the asthmatic lung, predominantly after IL-4 stimulation. Eotaxin-3 is therefore a marker of inappropriate airway inflammation. Polyphenolic (PP) compounds found in high concentrations in berries may have beneficial effects in inflammatory conditions. Plant and Food Research produced high-PP extracts of blackcurrant (BC) cultivars that were tested for inflammation modulating effects. Since high doses of PPs have been shown to cause cell death, we tested two BC cultivars at a range of concentrations in a cell viability (WST-1) assay. While no toxic effects were attributable to the BC extracts (1-50µg/ml), a dose-related trend in cell death was observed and therefore 10µg/ml was chosen for further experiments Ten BC cultivars were compared for efficacy by measuring eotaxin-3 production in IL-4 stimulated human lung epithelial (A549) cells in vitro. Cells were incubated with BC extracts (10µg/ml) and IL-4 (10ng/ml) for 24 hours. The supernatants were then quantified for eotaxin-3 levels by an enzyme-linked immunosorbent assay (ELISA). All ten BC extracts reduced eotaxin-3 levels after stimulation with IL-4, and six BC extracts were effective by statistically significant levels (P<0.05), (BC cultivars -01, -02, -03, -05, -09 & -10). Of those, BC extracts of four cultivars demonstrated a reduction of more than 65% from the IL-4 stimulated control. In addition, a positive trend in inflammation modulation vs. one anthocyanin (ACN) in the BC extracts was shown. This study has demonstrated the beneficial inflammation modulatory effects of polyphenolic BC extracts, which could be related to cyanidin 3-O-rutinoside content. These results may have therapeutic potential for asthma.

[Truncated abstract] Objective: To investigate the demographics, success rate of application, nature and frequency of complication and the survival outcome of patients receiving advanced airway management in the pre-hospital setting. Design: Prospective observational cohort study. Participants: Patients who were attended to by St. John Ambulance Paramedics in the Perth Metropolitan area and selected regional areas within Western Australia. The patients were unconscious, unresponsive with no gag reflex and where application of an advanced airway would improve ventilation. Methods: Ambulance Paramedics received mannequin training within the classroom environment on the techniques for the application of the Endo-Tracheal Tube and the Laryngeal Mask Airway. The indication for the application of an advanced airway was any patient whose ventilation may be improved by intubation. These patients would be either deeply unconscious and areflexic, long term transport, severely injured (especially head injured) or cardiac arrest patients. Results: ... Paramedic assessment demonstrated that 14 (7.4%) 3 patients had an improvement in outcome. Of the 14 patients, 5 (2.7%) cardiac arrest patients survived to discharge from hospital compared to a 2.1 % survival rate for all cardiac arrest cases attended by the WAAS in 2002. Conclusion: Ambulance Paramedics can successfully apply an advanced airway apparatus in the pre-hospital environment. There was no statistical significance to demonstrate whether the introduction of advanced airway skills was beneficial or detrimental to patient survival outcome.

Indiana University-Purdue University Indianapolis (IUPUI) / More than 300 million people world-wide suffer from breathlessness, wheezing, chest tightness, and coughing characteristic of chronic bronchial asthma, the global incidence of which is on the rise. Allergen-sensitization and challenge elicits pulmonary expression of chemoattractants that promote a chronic eosinophil-rich infiltrate. Eosinophils are increasingly recognized as important myeloid effectors in chronic inflammation characteristic of asthma, although few eosinophil molecular signaling pathways have successfully been targeted in asthma therapy. p21 activated kinases (PAKs), members of the Ste-20 family of serine/threonine kinases, act as molecular switches in cytoskeletal-dependent processes involved in cellular motility. We hypothesized that PAK1 modulated eosinophil infiltration in an allergic airway disease (AAD) murine model. In this model, Pak1 deficient mice developed reduced inflammatory AAD responses in vivo with notable decreases in eosinophil infiltration in the lungs and broncho-alveolar lavage fluids (BALF). To test the importance of PAK1 in hematopoietic cells in AAD we used complementary bone marrow transplant experiments that demonstrated decreased eosinophil inflammation in hosts transplanted with Pak1 deficient bone marrow. In in vitro studies, we show that eotaxin-signaling through PAK1 facilitated eotaxin-mediated eosinophil migration. Ablating PAK1 expression by genetic deletion in hematopoietic progenitors or siRNA treatment in derived human eosinophils impaired eotaxin-mediated eosinophil migration, while ectopic PAK1 expression promoted this migration. Together these data suggest a key role for PAK1 in the development of atopic eosinophil inflammation and eotaxin-mediated eosinophil migration.

Indiana University-Purdue University Indianapolis (IUPUI) / Carbon nanomaterials are widely produced and used in industry, medicine and scientific research. To examine the impact of exposure to nanoparticles on human health, the human airway epithelial cell line, Calu-3, was used to evaluate changes in the cellular proteome that could account for alterations in cellular function of airway epithelia after 24 h exposure to 10 μg/mL and 100 ng/mL of two common carbon nanoparticles, singleand multi-wall carbon nanotubes (SWCNT, MWCNT). After exposure to the nanoparticles, label-free quantitative mass spectrometry (LFQMS) was used to study differential protein expression. Ingenuity Pathway Analysis (IPA) was used to conduct a bioinformatics analysis of proteins identified by LFQMS. Interestingly, after exposure to a high concentration (10 μg/mL; 0.4 μg/cm2) of MWCNT or SWCNT, only 8 and 13 proteins, respectively, exhibited changes in abundance. In contrast, the abundance of hundreds of proteins was altered in response to a low concentration (100 ng/mL; 4 ng/cm2) of either CNT. Of the 281 and 282 proteins that were significantly altered in response to MWCNT or SWCNT, respectively, 231 proteins were the same. Bioinformatic analyses found that the proteins common to both kinds of nanotubes are associated with the cellular functions of cell death and survival, cell-to-cell signaling and interaction, cellular assembly and organization, cellular growth and proliferation, infectious disease, molecular transport and protein synthesis. The decrease in expression of the majority proteins suggests a general stress response to protect cells. The STRING database was used to analyze the various functional protein networks. Interestingly, some proteins like cadherin 1 (CDH1), signal transducer and activator of transcription 1 (STAT1), junction plakoglobin (JUP), and apoptosis-associated speck-like protein containing a CARD (PYCARD), appear in several functional categories and tend to be in the center of the networks. This central positioning suggests they may play important roles in multiple cellular functions and activities that are altered in response to carbon nanotube exposure. To examine the effect of nanotubes on the plasma membrane, we investigated the interaction of short purified MWCNT with model lipid membranes using a planar bilayer workstation. Bilayer lipid membranes were synthesized using neutral 1, 2-diphytanoylsn-glycero-3-phosphocholine (DPhPC) in 1 M KCl. The ion channel model protein, Gramicidin A (gA), was incorporated into the bilayers and used to measure the effect of MWCNT on ion transport. The opening and closing of ion channels, amplitude of current, and open probability and lifetime of ion channels were measured and analyzed by Clampfit. The presence of an intermediate concentration of MWCNT (2 μg/ml) could be related to a statistically significant decrease of the open probability and lifetime of gA channels. The proteomic studies revealed changes in response to CNT exposure. An analysis of the changes using multiple databases revealed alterations in pathways, which were consistent with the physiological changes that were observed in cultured cells exposed to very low concentrations of CNT. The physiological changes included the break down of the barrier function and the inhibition of the mucocillary clearance, both of which could increase the risk of CNT’s toxicity to human health. The biophysical studies indicate MWCNTs have an effect on single channel kinetics of Gramicidin A model cation channel. These changes are consistent with the inhibitory effect of nanoparticles on hormone stimulated transepithelial ion flux, but additional experiments will be necessary to substantiate this correlation.