Christine Douglass. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 76-86). / Bibliography --- p.5 / Summary --- p.6 / Chapter 1. --- Introduction --- p.8 / Chapter 1.1 --- The problem --- p.8 / Chapter 1.2 --- The purpose of the study --- p.10 / Chapter 1.3 --- Study Design --- p.11 / Chapter 2. --- Literature Review --- p.12 / Chapter 2.1 --- Bronchial hyperresponsiveness --- p.12 / Chapter 2.12 --- "Asthma, bronchial hyperresponsiveness and respiratory symptoms suggestive of asthma" --- p.13 / Chapter 2.2 --- Atopy --- p.17 / Chapter 2.3 --- Genetics and the environment --- p.21 / Chapter 2.4 --- Environmental influences --- p.24 / Chapter 2.41 --- Smoking --- p.24 / Chapter 2.42 --- Passive smoking --- p.25 / Chapter 2.43 --- Pollution --- p.28 / Chapter 2.44 --- Upper respiratory tract infection --- p.31 / Chapter 3 --- Hong Kong --- p.34 / Chapter 4. --- Ethical approval --- p.35 / Chapter 5 --- Methods --- p.36 / Chapter 5.1 --- Subjects and study period --- p.36 / Chapter 5.2 --- Questionnaires --- p.36 / Chapter 5.3 --- Bronchial provocation --- p.38 / Chapter 5.31 --- Agents for provocation --- p.38 / Chapter 5.311 --- Histamine --- p.39 / Chapter 5.312 --- Guidelines for the storage and preparation of histamine --- p.39 / Chapter 5.32 --- Route of administration --- p.39 / Chapter 5.321 --- Inhalation provocation tests --- p.40 / Chapter 5.33 --- Parameters used to measure response and expression of results --- p.41 / Chapter 5.34 --- Preconditions for bronchial provocation testing- nontechnical factors --- p.43 / Chapter 5.35 --- A rapid method for measurement of bronchial responsiveness --- p.43 / Chapter 5.351 --- Nebulizer output --- p.43 / Chapter 5.352 --- Histamine solution preparation --- p.44 / Chapter 5.353 --- Lung function measurement --- p.44 / Chapter 5.354 --- Challenge procedure --- p.44 / Chapter 5.4 --- Measurement of atopic status --- p.46 / Chapter 6 --- Expression and analysis of data --- p.48 / Chapter 7 --- Results --- p.51 / Chapter 7.1 --- Repeatability of questionnaires --- p.51 / Chapter 7.2 --- Results from questionnaires --- p.51 / Chapter 7.21 --- Lifetime symptoms --- p.51 / Chapter 7.22 --- Symptoms within the past year --- p.52 / Chapter 7.23 --- Classification of groups for random selection --- p.54 / Chapter 7.3 --- Nebulizer output --- p.54 / Chapter 7.4 --- Computer generated random selection --- p.55 / Chapter 7.5 --- "Recording of ""yes"" when unsure of answers" --- p.55 / Chapter 7.6 --- Univariate statistical analysis --- p.56 / Chapter 7.61 --- Bronchial hyperresponsiveness of asthma --- p.56 / Chapter 7.66 --- "Respiratory symptoms suggestive of asthma, bronchial hyperresponsiveness and doctors diagnosis of asthma" --- p.58 / Chapter 7.67 --- Air quality and passive smoking --- p.58 / Chapter 7.68 --- Place of birth --- p.58 / Chapter 8. --- Discussion --- p.60 / Chapter 9. --- Conclusion and Recommendations --- p.73 / Acknowledgements --- p.75 / References --- p.76 / Tables --- p.87 / Figures --- p.113 / Appendix --- p.119

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Diss. Linköping : Univ., 2003.

Dados mostram que o aparecimento do diabetes mellitus (DM), em pacientes previamente asmáticos, diminui os sintomas da asma, enquanto a insulina agrava a asma. Devido a dados na literatura e por dados prévios do nosso grupo, o presente estudo teve como objetivo avaliar o efeito modulatório da insulina na inflamação alérgica pulmonar em camundongos diabéticos e saudáveis. Camundongos machos dibéticos BALB/c (aloxana, 50mg/kg, iv, 10 dias) foram sensibilizados com ovalbumina (OVA, 20 µg e Al (OH)3, 2 mg) 10 dias após a injeção de aloxana e uma dose reforço foi dada, após 12 dias da primeira de sensibilização, após 6 dias da dose reforço, os animais foram expostos a nebulização durante 7 dias com solução de OVA (1mg/mL) ou solução salina (SAL). Animais diabéticos foram tratados com doses múltiplas de Protamine Hagedorn Neutro (NPH) 2UI e 1UI, respectivamente, por via subcutânea 12 horas antes do desafio com OVA (às 19h) e 1UI (às 7h) 2h antes de cada desafio com OVA. Os animais não diabéticos receberam 1UI de insulina, pela mesma via 2h antes de cada desafio (às 7h), 24h após o último desafio, realizaram-se as seguintes análises: a) expressão de proteína quinase p38, proteína quinase regulada por sinais extracelulares 1 e 2 (ERK 1/2), proteína quinase ativada por estresse ou c-jun NH2- terminal (JNK) , transdutor de sinal e ativador de transcrição 3 (STAT 3) e transdutor de sinal e ativador de transcrição 6 (pSTAT 6) no homogenato de pulmão; b) perfil de imunoglobulinas presentes no soro; c) concentrações de interleucina (IL) IL-4, IL-5, IL-10, IL-13, fator de necrose tumoral alfa (TNF-α), fator de crescimento endotelial vascular (VEGF), fator de crescimento transformador beta (TGF-β) e interferon-gamma IFN-γ em homogenato de pulmão; d) migração celular em fluído do lavado broncoalveolar (LBA); e) perfil de células imunes na medula óssea, pulmão, timo e baço; f) mecânica pulmonar por BUXCO e FlexiVent. Em comparação com camundongos não diabéticos desafiados com OVA, os animais diabéticos desafiados com OVA mostraram diminuição em: ERK 1, ERK 2, JNK (fosfo54), JNK / SAPK, STAT3, pSTAT6 estava ausente; concentração da imunoglobulinas IgE, IgG1; perfil de citocinas Th2 como IL-4, IL-5, IL-13, TNF-α, VEGF, TGF-β; infiltrado inflamatório e) ausência de eosinofilia no LBA; células T, células B e eosinófilos na medula óssea, pulmão, timo e baço, e hiper-reatividade das vias aéreas. O tratamento com insulina restaubeleceu todos os parâmetros estudados. Portanto, sugerem que a insulina modula a inflamação alérgica pulmonar tardia em camundongos diabéticos. / Data show that the onset of diabetes mellitus (DM) in previously asthmatic patients decreases asthma symptoms while insulin worsens asthma. Due to data in the literature and previous data from our group, the present study aimed to evaluate the modulatory effect of insulin on pulmonary allergic inflammation in diabetic and healthy mice. Ovalbumin (OVA, 20 µg and Al (OH)3, 2 mg) were sensitized at 10 days after alloxan injection and a booster dose was given , after 12 days of the first sensitization, after 6 days of booster dose, the animals were exposed to nebulization for 7 days with OVA solution (1mg / mL) or saline solution (SAL). Diabetic animals were treated with multiple doses of Protamine Hagedorn Neutral (NPH) 2UI and 1UI, respectively, subcutaneously 12 hours prior to challenge with OVA (at 7pm) and 1UI (at 7h) 2h before each challenge with OVA. Non-diabetic animals received 1UI of insulin, via the same route 2h before each challenge (at 7h), 24h after the last challenge, the following analyzes were performed: a) expression of protein kinase p38, protein kinase regulated by extracellular signals 1 and 2 (ERK 1/2), stress-activated or c-jun NH2-terminal protein kinase (JNK), signal transducer and transcriptional activator 3 (STAT 3) and signal transducer and transcriptional activator 6 (pSTAT 6) in the lung homogenate; b) profile of immunoglobulins present in serum; c) concentrations of interleukin (IL) IL-4, IL-5, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), transforming TGF-β) and interferon-gamma IFN-γ in lung homogenate; d) cell migration in bronchoalveolar lavage fluid (BAL); e) profile of immune cells in the bone marrow, lung, thymus and spleen; f) Pulmonary mechanics by BUXCO and FlexiVent. In contrast to non-diabetic mice challenged with OVA, diabetic animals challenged with OVA showed decrease in: ERK 1, ERK 2, JNK (phospho54), JNK / SAPK, STAT3, pSTAT6 was absent; IgE immunoglobulin levels, IgG1; profile of Th2 cytokines such as IL-4, IL-5, IL-13, TNF-α, VEGF, TGF-β; inflammatory infiltrate e) absence of eosinophilia in BAL; T cells, B cells and eosinophils in the bone marrow, lung, thymus and spleen, and airway hyperreactivity. The insulin treatment restored all parameters studied. Therefore, they suggest that insulin modulates late pulmonary allergic inflammation in diabetic mice.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from PDF title page (viewed on Feb. 4, 2010). Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 124-138). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Com o objetivo de verificar a influÃncia dos hormÃnios tireoideanos no desenvolvimento de hiperreatividade traqueal, ratos machos (200 - 250 g) eutireÃideos, hipotireÃideos (propiltiouracil [PTU] - v.o. 0,05% p/v, durante 4 semanas) ou hipertireÃideos (L- tiroxina [T4] - 0,5 mg/kg s.c., por 7 ou 9 dias) foram sensibilizados à ovalbumina (OVA) e, 14 dias depois, desafiados atravÃs da inalaÃÃo de OVA (1 mg/ml, seguida de 5 mg/ml, 15 min cada). O sacrifÃcio dos animais para a realizaÃÃo dos experimentos ocorreu 24 h apÃs o desafio antigÃnico por anestesia com hidrato de cloral (400 mg/Kg). A traquÃia isolada foi montada em cubas contendo 10 ml de Krebs-Henseleit modificado (37 oC, 5% de CO2 em O2). Foram obtidas curvas concentraÃÃo-efeito (CCE) para cloreto de potÃssio (KCl), carbacol (CCh) ou serotonina (5-HT). TambÃm foram realizadas CCE ao Ca2+ em preparaÃÃes estimuladas por KCl, CCh ou 5-HT e mantidas em soluÃÃo sem Ca2+. A reapresentaÃÃo do antÃgeno promoveu significativo aumento (p < 0,05, two-way ANOVA) da resposta mÃxima (RM) das CCE ao KCl de 0,96  0,10 gF para 1,53  0,11 gF (n = 7), ao CCh de 1,98  0,06 gF para 2,92  0,07 gF (n = 7) e à 5-HT de 1,64  0,14 gF para 2,41  0,15 (n = 6) nos tecidos obtidos de animais sensibilizados ou desafiados, respectivamente. As traquÃias tambÃm apresentaram aumento (p < 0,05, two-way ANOVA) da RM ao Ca2+ quando estimuladas com KCl de 0,54  0,06 gF para 0,86  0,07 gF (n = 6), com CCh de 1,20  0,14 gF para 1,77  0,14 gF (n = 6) ou com 5-HT de 0,59  0,10 gF para 1,15  0,05 gF (n = 6) nos tecidos obtidos de animais sensibilizados ou desafiados, respectivamente. O hipotireoidismo nÃo alterou significativamente a RM induzida por KCl e CCh, enquanto que aquela induzida pela 5-HT foi reduzida de 1,64  0,14 gF nos animais eutireÃideos para 0,34  0,07 gF nos animais hipotireÃideos (p < 0,001, two-way ANOVA). ApÃs desafio, a 5-HT produziu 0,56  0,11 gF (n = 7) no tecido hipotireÃideo (p < 0,001, two-way ANOVA). O hipotireoidismo aboliu o desenvolvimento de hiperreatividade para KCl e CCh. Ocorreu um aumento na CE50 nas CCE obtidas ao CCh de 0,49 x 10-6M para 4,65 x 10-6M (P < 0,05, two-way ANOVA ). O desafio reduziu a CE50 novamente para 1,53 x 10-6M (n = 6, p<0,05, two-way ANOVA). As traquÃias de animais hipotireÃideos desafiados apresentaram diminuiÃÃo da RM ao Ca2+ quando estimuladas com KCl, CCh e 5-HT. Ocorreu aumento na CE50 nas CCE ao Ca2+ em traquÃias desafiadas e estimuladas com CCh de 5,77 x 10-4 M para 22,50 x 10-4 M (n = 6, p<0,01 two-way ANOVA). O hipertireoidismo promoveu um significativo aumento na RM das CCE apenas ao KCl (0,96  0,10 gF no controle versus 1,58  0,15 no tecido hipertireÃideo). NÃo houve desenvolvimento de hiperreatividade apÃs o desafio antigÃnico (RM = 1,87  0,14 gF). Ocorreu diminuiÃÃo da CE50 ao CCh de 0,67 x 10-4 M no controle para 0,14 x 10-4 M apÃs tratamento com T4. Os resultados mostram que hà envolvimento dos hormÃnios tireoideanos no desenvolvimento de hiperreatividade em traquÃia de rato, induzida apÃs reapresentaÃÃo do antÃgeno a animais previamente sensibilizados. / In other to verify the influence of thyroid hormones on the tracheal hyperreactivity development, euthyroid, hypothyroid (propiltiouracil [PTU] - p.o. 0.05% w/v, 4 weeks) or hyperthyroid (L-tiroxine [T4] â 0.5 mg/kg s.c.,7 or 9 days) male rats (200 - 250 g) were sensitized to ovalbumine (OVA) and, 14 days later, challenged with OVA inhalation, (1 mg/ml, followed by 5 mg/ml, 15 min each). Animals sacrifice was carried out 24 later by means of anaesthesia with chloral hydrate (400 mg/Kg). Isolated trachea was mounted in 10 ml bath chamber filled with modified Krebs-Henseleit (37 oC, 5% de CO2 em O2). Concentration-effect curves (CEC) were carried out for potassium chloride (KCl), carbachol (CCh) or serotonin (5-HT). CEC to Ca2+ added in tissues maintained in Ca2+-free medium stimulated with KCl, CCh or 5-HT also were carried out. Antigenic challenge produced significant increase (p < 0.05, two-way ANOVA) of the maximal response (Emax) of the CCE for KCl from 0.96  0.10 gF to 1.53  0.11 gF (n = 7), for CCh from 1.98  0.06 gF to 2.92  0.07 gF (n = 7) and for 5-HT from 1.64  0.14 gF to 2.41  0.15 (n = 6) in tissues obtained from sensitized or challenged animals, respectively. Tracheae also showed increase on the Emax to Ca2+ (p < 0.05, two-way ANOVA) when stimulated with KCl from 0.54  0.06 gF to 0.86  0.07 gF (n = 6), with CCh from 1.20  0.14 gF to 1.77  0.14 gF (n = 6) or with 5-HT from 0.59  0.10 gF to 1.15  0.05 gF (n = 6) on sensitized or challenged tissues, respectively. The hypothyroidism did not modify significantly the KCl- or CCh-induced Emax, while the 5-HT-induced contractile effect was reduced from 1.64  0.14 gF in euthyroid tissues to 0.34  0.07 gF in hypothyroid tissues (p < 0.001, two-way ANOVA). After challenge, 5-HT produced in hypothyroid tissues a contraction corresponding to 0.56  0.11 gF (n = 7, p < 0.001, two-way ANOVA). Hypothyroidism prevented hyperreactivity development for KCl and CCh. It was observed an increased EC50 value in CCE for CCh from 0.49 x 10-6M to 4.65 x 10-6 M (p < 0,05, two-way ANOVA). After challenge, CE50 value was reduced to 1.53 x 10-6 M (n = 6, p < 0,05, two-way ANOVA). Tracheae from challenged hypothyroid animals showed decreased Emax to Ca2+ when they were stimulated with KCl, CCh and 5-HT. It was observed an increased EC50 value in CCE to Ca2+ in challenged tissues stimulated with CCh from 5.77 x 10-4 M to 22.50 x 10-4 M (n = 6, p < 0.01, two-way ANOVA). Hyperthyroidism significantly increased Emax of the KCl-induced CCE (0.96  0,10 gF in control versus 1.58  0.15 on hyperthyroid tissue). Hyperreactivity was not showed after antigenic challenge (Emax = 1.87  0.14 gF). It was observed a reduction of the EC50 value to CCh from 0.67 x 10-4 M in control to 0.14 x 10-4 M after T4 treatment. Our results show that there is a putative thyroid hormones involvement in hyperreactivity development on rat trachea, after an antigenic challenge.