Atopic dermatitis (AD) typically develops in patients with a history of allergic ailments, and is characterised by an itchy, inflammatory skin condition with scaling, lichenification, papules, excoriations and pruritus. In AD patients a chronic relapsing inflammatory condition is seen, associated with IgE hyper production. AD flares are largely triggered by environmental factors. However, the exact etiology of AD is unclear and there is a pressing need for new treatment regimens as AD is a chronic condition and requires long term treatment. Historically Aloe has been used to treat skin conditions as well as a variety of other diseases. To further explore the pathogenesis and treatment of AD, Balb/c mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB) for atopic dermatitis induction. Thereafter, mice were treated with either Aloe ferox or Aloe vera applied daily on the dorsal skin for 10 consecutive days. A placebo gel was used for the control mice. Blood was collected at the end of the treatment period and serum IgE levels measured. Serum IgE levels were significantly lowered in the Aloe ferox group than in the Aloe vera group. This study demonstrated Aloe’s immunoregulatory potential for alleviating atopic dermatitis through influencing of Th2 cell activation. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Pharmacology / unrestricted

Maintaining of homeostasis is essential for the survival of the organism. Stress disturbs the homeostasis and prepares the organism for mental or physical stress. During the stress situation, the endogenous stress factors are released. Through these factors stress affects tissue regeneration, the immune system and other metabolic processes. Chronic stress impacts many parts of body and mind and has a negative effect on these processes. Acute stress has the opposite effect. Mesenchymal stem cells (MSCs) participate in regenerative processes and modulate the immune system. Therefore, it can be assumed that stress will affect on MSCs. The aim of this study was to investigate the effect of stress factors, norepinephrine and corticosterone on the properties and function of MSCs in acute and chronic stress model. In our study, stress factors did not affect the morphology, vitality and differentiation of MSCs. However, the metabolic activity of MSCs was reduced regardless of the duration of their action. The action of stress factors also affected the production of some immunologically relevant molecules and proteins. Unfortunately, the results did not show a clear effect of stress factors on the lymphocyte modulation by MSCs. Key words: mesenchymal stem cells, catecholamines, adrenergic receptors,...

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.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18852号 / 医博第3963号 / 新制||医||1007(附属図書館) / 31803 / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 中原 俊隆, 教授 山田 亮 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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.

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Although glucocorticoids are often used as an adjunct to epinephrine to treat anaphylactic shock, glucocorticoids can also be a rare cause of anaphylactic shock. Only through the administration of a challenge dose of different glucocorticoids and different substrates that glucocorticoids are delivered in can the determination be made about which glucocorticoid or accompanying solvent may be the culprit which caused the anaphylactic reaction. These challenge tests should only be performed in a controlled environment as repeat anaphylaxis is a risk, especially if the patient has a history of glucocorticoid-induced anaphylaxis.

Objective: Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. Study Design: We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids (MACS) for Preterm Birth trial. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotising enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. Multivariable regression analyses were conducted with adjustment for pre-defined covariates including an interaction between exposure to ACS and infant sex. Results: Data on 2304 infants were analyzed. The interaction term between treatment status (multiple courses versus a single course of ACS) and infant sex was not significant in the adjusted model for the primary outcome (p=0.86), nor for any of the secondary outcomes. Exposure to multiple courses versus a single course of ACS was not associated with the primary outcome either before or after adjustment (aOR 0.99, 95% CI 0.67 to 1.45, n=2292 infants). However, exposure to multiple courses versus a single course of ACS resulted in significantly lower birth length (p=0.02) and head circumference at birth (p=0.04) although not birthweight (p=0.06). Conclusions: Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention. / Thesis / Master of Science (MSc) / Antenatal corticosteroids (ACS) are given in pregnancies at risk of early birth. ACS help the lungs and other organs, such as the brain and kidneys to mature. ACS help improve babies’ survival and reduce the risk of other health complications. Several animal studies suggest that infant sex can affect long-term outcomes after receiving a higher dose of ACS. The goal of our study was to look at the effect of infant sex on the relationship between the use of multiple courses (i.e., a higher dose) versus a single course of ACS and short-term outcomes. These outcomes include challenges with breathing, bleeding in the brain, problems in the bowel, and infant death. Our study found that infant sex did not significantly change the relationship between ACS and short-term infant outcomes, but further study is required on long-term outcomes as sex specific differences may emerge over time as reported in animal literature.