This thesis is part of a larger series of studies being conducted by Kristine Tanner, PhD, Associate Professor in the Department of Communication Disorders at Brigham Young University (BYU). The larger project is funded by the National Institute on Deafness and Other Communication Disorders at the National Institutes of Health. This thesis primarily investigated the effects of combination inhaled corticosteroids (ICs) on aerodynamic measures of the voice. In recent years, an increase in the localized laryngeal side effects from IC treatment, including dysphonia, have been reported. This study employed a between-groups experimental design, with two groups of rabbit larynges having been exposed to either ICs or nebulized isotonic saline two times each day for eight weeks at The University of Utah. For this study, the independent variable is group condition (i.e., IC versus saline) and the dependent variables are two aerodynamic measurements made at the onset of phonation using a benchtop experimental setup, namely phonation threshold pressure (PTP; cmH2O) and phonation threshold flow (PTF; L/min). The results of this study indicate a significant difference in PTP and PTF between vocal folds treated with IC as compared to vocal folds treated with nebulized isotonic saline solution. Implications of this study suggest negative changes in the voice due to IC treatment.

The purpose of this thesis is to examine the effects of inhaled corticosteroid drugs (ICs) on the voice due to their frequent use in treating an increasing prevalence of asthma disorders. As part of a larger five-year study, the focus of this thesis is specifically on whether 8 weeks of in vivo exposure to ICs will cause changes in the sustained subglottal pressure, sustained airflow, and visual-perceptual ratings of edema and erythema in excised rabbit larynges. Researchers administered either ICs or a control nebulized isotonic saline solution to 22 rabbits in vivo, sacrificed them, and harvested their larynges for benchtop research. While ensuring proper tissue preservation, researchers then finely dissected the larynges to expose the true vocal folds and run phonation trials. Dependent variables included continuous acoustic signals (Hz), subglottal pressure (cm H2O), and airflow (L/min) data for 15 phonation trials per rabbit larynx. Researchers also collected still image photographs at this time and subsequently normalized them for use in the visual-perceptual portion of this thesis. For visual-perceptual ratings, raters used a 0-3 equal appearing interval scale to rate aspects of edema and erythema on left and right vocal fold and arytenoid tissues. Results indicate that, when compared to control larynges exposed to nebulized isotonic saline, experimental larynges treated with ICs require significantly higher subglottal pressure to maintain phonation, p < .05. Mean sustained phonation for experimental larynges is 11.24 cm H2O compared to 8.92 cm H2O for that of control larynges. Phonation trials for experimental larynges have significantly higher sustained airflow with a mean of 0.09 L/min compared to 0.07 L/min for that of control larynges, p < .05. Surprisingly, experimental larynges have higher average fundamental frequencies with less variability (mean: 519 Hz, standard deviation: 66 Hz) than that of control larynges (mean: 446 Hz, standard deviation: 130 Hz). On visual-perceptual ratings, experimental larynges have significantly higher severity ratings on all eight items rated, p < .0001 - p = .0305. Based on these results, it is concluded that ICs cause significant damage to rabbit vocal folds, as evidenced by higher sustained pressure, higher airflow, and higher severity ratings for experimental versus control larynges. The dependent variables in this thesis are novel in benchtop model research and demonstrate a unique perspective on this research question. Thus, this thesis informs future phonation, benchtop, and visual-perceptual research.

In an effort to elucidate the mechanism by which indomethacin (IN) lessens the stimulatory effect of estradiol (E2) on rabbit splenic red pulp macrophages (RPMs), 39 female New Zealand White rabbits were divided into 10 groups: ovariectomized (OVX) and OVX/ IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX) and SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2 and OVX/25 mg E2/IN at 0.1 and 5.0 mg/kg bw/day; and intact control. Changes in RPM population in response to treatment were measured using a 0-4 histologic grade. Estradiol treatment resulted in increased RPM grade when compared to the OVX groups. Indomethacin addition lowered mean RPM grade in the SOVX/IN 5.0 group when compared to its E2 control group. Indomethacin administration had no significant effect on levels of prostaglandin E 2 in spleen, urine, or blood. Hematocrits were reduced in both OVX and OVX/E2 groups; this decrease was exacerbated by the high IN dose. In summary, the results from this study suggest that the effect of IN on E2-induced RPM activation may be mediated through a nonprostaglandin pathway. The observed hematocrit changes are possibly the result of direct action of IN and E2 on erythrocytes, resulting in their accelerated clearance from the circulation by splenic RPM.

The effects of stimulation of the A5 cell group of the caudal ventrolateral pons electrically or with L-glutamate on heart rate and blood pressure were determined in rabbits. Electrical stimulation caused blood pressure increases and reflex bradycardia. L-glutamate caused decreases in blood pressure and heart rate which were blocked by the L-glutamate antagonist aminophosphoheptanoic acid. Transection of the brainstem at the level of the midbrain did not alter the effects of either electrical or chemical stimulation. Lesions of the nucleus and tractus solitarius (NTS) attenuated the effects of L-glutamate, but did not change the effectiveness electrical stimulation. Injections of 6-hydroxydopamine three to four weeks before the experiments blocked the effects of electrical stimulation but only reduced the effects of L-glutamate injection. The A5 group may have two functional subdivisions. Some A5 cells may produce blood pressure depressor and bradycardiac effects by means of projections to the NTS and the spinal cord. Other A5 cells may produce blood pressure presser effects by means of projections to the spinal cord.

The expression of the α1C-adrenoceptor subtype in human and rabbit blood vessels has been analyzed using the reverse transcriptase/polymerase chain reaction technique (RT/PCR). The 20 bp primers employed were designed from the bovine α1C-adrenoceptor and flank a least conserved region - the putative third cytoplasmic loop. RT/PCR products generated from rabbit and human brain mRNA both had 93% homology to the bovine α1C-adrenoceptor and were used as species and subtype specific probes in Southern blot analysis of vascular RT/PCR products. Poly A+ RNA was purified from the human saphenous vein and rabbit aorta, renal, pulmonary and central ear arteries and amplified by RT/PCR. Size analysis by agarose gel electrophoresis, together with Southern hybridization of the resulting cDNA products confirm the expression of the α1C-adrenoceptor in these vessels.

La pollution atmosphérique est un problème de santé publique majeur responsable en 2012 de 3,7 millions de décès prématurés dans le monde. La pollution de l’air, au même titre que les autres facteurs environnementaux (e.g., nutrition, stress) auxquels sont exposées les femmes enceintes, pourrait avoir un impact sur le développement foetal. L’objectif de ce travail était d’étudier les effets d’une exposition gestationnelle aux gaz d’échappement de moteur diesel, source majeure de la pollution atmosphérique, sur le développement foetoplacentaire en première (F1) et deuxième (F2) génération. Des lapines gestantes (F0) ont été exposées 2h/jour du 3e au 27e jour post-conception (jpc) à des niveaux de gaz d’échappement de moteur diesel mimant un pic de pollution aux particules fines de grandes villes européennes. L’exposition gestationnelle des lapines F0 entrainait des signes d’hypotrophie foetale (réduction de la longueur de la tête, de l’efficacité placentaire et hypoinsulinémie des foetus F1 à 28jpc) associés à un défaut de vascularisation placentaire et des dérégulations fonctionnelles du placenta identifiées par une analyse d’enrichissement de réseaux de gènes (GSEA) sur des données de transcriptomique (microarray dédié). Le transfert transplacentaire des nanoparticules inhalées a été démontré par microscopie électronique à transmission. En F2, la concentration plasmatique en triglycérides était réduite et la concentration plasmatique en cholestérol augmentée chez les foetus issus des lapines F1 exposées in utero. La biométrie foeto-placentaire et la structure du placenta n’ont pas été affectées. Les analyses GSEA du transcriptome placentaire F2 ont révélé des perturbations de réseaux de gènes impliqués dans la formation du protéasome et desexosomes et dans l’inflammation. Les modulations de profils en acides gras au niveau placentaire et fœtal suggèrent la mise en place de mécanismes adaptatifs anti-inflammatoires chez les F2. En conclusion, l’exposition gestationnelle chronique à des gaz d’échappement de moteur diesel induit des perturbations foeto-placentaires sur plusieurs générations. Ces données ont mis en évidence le risque lié aux nanoparticules émises par les moteurs diesel et qui ne sont soumises actuellement à aucune réglementation. / Atmospheric pollution is a major threat for human health, causing 3.7 million premature deaths worldwide in 2012. Air pollution, as well as other environmental factors (e.g., nutrition, stress) faced by pregnant women may affect fetal development. The objective of this work was to study the impact of gestational exposure to diesel engine exhaust (DE), a major source of air pollution, on the fetoplacental development in the first (F1) and second (F2) generation. Pregnant rabbits (F0) were exposed 2h/day from 3 to 27 days post-conception (dpc) at DE levels mimicking a pollution peak in major European cities. Gestational exposure of F0 females induced signs of fetal hypotrophia (reduced head length, placental efficiency and hypoinsulinemia in fetuses at 28 dpc) associated with placental vasculature failure and placental functional deregulations identified by gene set enrichment analysis (GSEA) on transcriptomic data (dedicated microarray). Transplacental transfer of inhaled nanoparticles was demonstrated by transmission electronic microscopy. In F2 generation, plasma triglyceride concentrations were reduced and plasma cholesterol concentration increased in fetuses of in utero exposed F1 rabbits. Placental biometry and structure were not affected. GSEA analysis of F2 placental transcriptome revealed disturbances in gene networks involved in formation of proteaome and exosome, in inflammation. Modulations of placental and fetal fatty acid profiles suggest anti-inflammatory adaptive mechanisms in F2 fetuses. In conclusion, chronic gestational exposure to diesel engine exhaust affects fetoplacental development over several generations. These data highlight health hazards caused by DE nanoparticles and currently not subject to regulation.

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The purpose of this thesis is to investigate the reversibility of the adverse effects of combination inhaled corticosteroids (ICs) on vocal fold health as part of a five-year study. This pilot study tested the hypothesis that the adverse effects of ICs may be induced and then reversed, using a benchtop model and rabbit larynges measuring sustained subglottic pressure and airflow. Eighteen rabbits were assigned randomly to 5 subgroups, including baseline, induction experimental, induction control, reversibility experimental, and reversibility control. Baseline rabbits did not receive any treatment. Both experimental groups, induction and reversibility, were administered Advair until visual-perceptual ratings were noted. Their paired control groups were administered nebulized saline in the same dosage levels. Induction groups were immediately sacrificed, while reversibility groups entered a withdrawal phase until visual-perceptual ratings showed a return to baseline. Larynges were dissected and mounted on a benchtop model for phonation trials. Dependent variables included sustained phonatory pressure (cm/H2O) and sustained phonatory airflow (L/min). The results of phonation trials indicate that sustained pressure and flow were higher for both induction and reversibility experimental groups when compared to baseline and control groups. The reversibility experimental group had lower sustained pressure and flow than the induction experimental group. These results indicate a reduction of signs after a period of rest. These findings suggest that voice symptoms may be reversible to a degree after combination IC use. These are important preliminary data that support future studies with larger sample sizes to confirm findings.

This diploma thesis Insight brings philosophical reflection on photographic media in the form of installation with video-projection in space. Issues over problems of photographic media (locked doubles, stopped time, framed imprint of reality, real raw depiction) are opening by using story about creation of picture of a rabbit on the moon in the style of open metaphors in a white room. Through this myth photographic medium gets the concrete form - in the form of symbolic environment with objets and signs. The whole work is free personification of photograph in whose inside the audience may find themselves.