Mycoplasma gallisepticum (MG) can cause chronic respiratory disease in chickens and infectious sinusitis in turkeys. Impacts of MG infections can include increased morbidity and mortality, decreased egg production, hatchability and feed efficiency. Biosecurity and bio-surveillance remain the primary means of deterrence as the current means of control are not wholly effective. Further applications towards the characterization of MG-related disease control requires proper understanding of the characteristics of MG infections with accurate and efficient quantification of in vivo MG populations. To this end, study was conducted to determine the in vivo MG populations in infected pullets and to determine impact of sampling schedule. The role of sampling in 3 distinct anatomical sites, and their associated MG populations were also compared. Results confirmed that sampling events did not affect MG populations and as a possible confounding factor, sampling frequency could be avoided for the future development of novel means of MG control.

Indiana University-Purdue University Indianapolis (IUPUI) / The contractile activation of airway smooth muscle tissues stimulates actin polymerization and the inhibition of actin polymerization inhibits tension development. Actin depolymerizing factor (ADF) and cofilin are members of a family of actin–binding proteins that mediate the severing of F–actin when activated by dephosphorylation at serine 3. The role of ADF/cofilin activation in the regulation of actin dynamics and tension development during the contractile activation of airway smooth was evaluated in intact canine tracheal smooth muscle tissues. Two–dimensional gel electrophoresis revealed that ADF and cofilin exist in similar proportions in the muscle tissues and that approximately 40% of the total ADF/cofilin in unstimulated tissues is phosphorylated (inactivated). Phospho–ADF/cofilin decreased concurrently with tension development in response to stimulation with acetylcholine (ACh) or potassium depolarization indicating the activation of ADF/cofilin. Expression of an inactive phospho–cofilin mimetic (cofilin S3E), but not WT cofilin in the smooth muscle tissues inhibited endogenous ADF/cofilin dephosphorylation and ACh–induced actin polymerization. Expression of cofilin S3E in the tissues depressed tension development in response to ACh, but it did not affect myosin light chain phosphorylation. The ACh–induced dephosphorylation of ADF/cofilin required the Ca2+–dependent activation of calcineurin (PP2B). Expression of Slingshot (SSH) inactive phosphatase (C393S) decreased force development and cofilin dephosphorylation. Activation of ADF/cofilin was also required for the relaxation of tracheal muscle tissues induced by forskolin and isoproterenol. Cofilin activation in response to forskolin was not Ca2+–dependent and was not inhibited by calcineurin inhibitors, suggesting it was regulated by a different mechanism. Cofilin activation is required for actin dynamics and tension development in response to the contractile stimulation of tracheal smooth muscle and is regulated by both contractile and relaxing stimuli. These concepts are critical to understanding the mechanisms of smooth muscle contraction and relaxation, which may provide novel targets for therapeutic intervention in the treatment of abnormal airway responsiveness.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25488号 / 医博第5088号 / 新制||医||1073(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 後藤 慎平, 教授 平井 豊博, 教授 浅野 雅秀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Contexte – La stimulation de la muqueuse trachéale peut provoquer une réponse défensive à type de toux. La finalité de cette réponse est la protection des voies aériennes via la clairance du mucus et des particules déposées au sein de l’arbre trachéo-bronchique. La stimulation de la muqueuse nasale est à l’origine de réponses défensives n’incluant toutefois pas la toux. La modulation de la toux suggère de possibles interactions centrales des afférences provenant de localisations anatomiques distinctes. Objectif – Déterminer si une stimulation trachéale mécanique discriminante est capable de provoquer une toux lors d’une apnée provoquée par l’instillation nasale d’eau distillée. Méthodes – Douze lapins anesthésiés et trachéotomisés ont été étudiés. Les stimulations trachéales mécaniques ont été réalisées dans 3 conditions : contrôle, après instillation nasale de sérum physiologique, et lors d’apnée suite à l’instillation d’eau distillée. Résultats – Les paramètres ventilatoires de références ne sont pas différents dans les 3 conditions. Un total de 171 stimulations trachéales a été réalisé. Lors de l’apnée, 81% des réponses sont des réflexes expiratoires et le pic de débit expiré est inférieur (p < 0.0001) à celui observé dans les conditions contrôle et sérum physiologique. L’incidence des réponses comprenant un réflexe de toux est plus faible (p < 0,0001) en cas d’instillation d’eau distillée que dans les 2 autres conditions.Conclusion – La stimulation nasale par l’eau distillée désensibilise les réflexes de défense respiratoire faisant suite à une stimulation trachéale mécanique / Context - Cough may be triggered by irritation of afferents located in the airway mucosa. Primary role is to expel inhaled foreign matter from the lungs or clear the airways of endogenous mucus. Stimulation of the nasal mucosa provokes defensive responses but not cough. The ‘cough center’ can be tuned by various afferent inputs, suggesting possible interactions at a central level of neural pathways originating from distant anatomical sites. Objective - The present study was designed to determine whether brief mechanical stimulation of the trachea could trigger cough during apnoea elicited by nasal instillation of water. Method - Twelve anesthetized, tracheotomized rabbits were studied. Mechanical stimulation of the trachea was performed under 3 conditions: baseline control, after instillation of saline into the nose and during apnoea following instillation of water. Results - Baseline breathing pattern did not differ between the 3 conditions. In a series of 171 stimulations, expiration reflex occurred in 81% of stimulations during apnoea with a significantly (p < 0.0001) lower peak expiratory flow than at baseline or during saline instillation. The incidence of responses comprising a cough reflex was also lower during water instillation than at either baseline or with saline (p < 0.0001). Conclusion - These results indicate that stimulation of nasal afferents with distilled water likely down-regulates cough

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2018-07-09T11:18:39Z No. of bitstreams: 2 Dissertação - Marco Túlio Lacerda Ribeiro - 2018.pdf: 1380967 bytes, checksum: 194ed48e2af9c60ef94be3f60db75ef7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-07-09T11:27:43Z (GMT) No. of bitstreams: 2 Dissertação - Marco Túlio Lacerda Ribeiro - 2018.pdf: 1380967 bytes, checksum: 194ed48e2af9c60ef94be3f60db75ef7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-07-09T11:27:43Z (GMT). No. of bitstreams: 2 Dissertação - Marco Túlio Lacerda Ribeiro - 2018.pdf: 1380967 bytes, checksum: 194ed48e2af9c60ef94be3f60db75ef7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-06-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Background: Some studies relate the use of paracetamol with the exacerbation of asthma symptoms and other respiratory problems. Other studies are inconclusive or deny this correlation. This makes the association between paracetamol and airway hypersensitivity very controversial and still under debate. Objectives: To investigate the effect of chronic treatment with paracetamol on rats on the contraction and relaxation of isolated airways. Methods: Wistar rats were divided into 2 groups (n = 5-8). One group was treated for 2 weeks with paracetamol (400 mg / kg, v.o.) in drinking water and another control group (pure water). The animals were euthanized after two weeks, blood was collected for biochemical analyzes (ALT, AST, TBARs reaction) and tracheal rings were isolated and prepared in an organ bath to measure the isometric tension against contractile stimuli (concentration- effect for carbachol and KCl, concentration- 2+ effect curve for Ca stimulated with carbachol or KCl) and relaxants (isoprenaline, sodium nitroprusside and verapamil). Results: Liver enzymes ALT, AST and lipid peroxidation (TBARs) were significantly increased after paracetamol treatment. Acupuncture of the airway tracheal smooth muscle response does not present any alteration, either to the contractile or relaxing stimulus, for example: cholinergic agonist, membrane 2+ 2+ 2+ depolarization, Ca influx by the sarcolemma, internal release of Ca from the sarcoplasmic reticulum, Ca , β-receptor agonist or NO donor-induced relaxation. Conclusion: Chronic treatment with paracetamol does not induce hyper or hyporeativity of the airways isolated from rats. / Introdução: Alguns estudos relacionam o uso de paracetamol com a exacerbação dos sintomas da asma e outros problemas respiratórios. Outros estudos não são conclusivos ou negam essa correlação. Isso torna a associação entre o paracetamol e a hipersensibilidade das vias aéreas muito controversa e ainda em debate. Objetivos: Investigar o efeito do tratamento crônico com paracetamol em ratos sobre a contração e relaxamento de vias aéreas isoladas. Métodos: Ratos Wistar foram divididos em 2 grupos (n=5-8). Um grupo foi tratado por 2 semanas com paracetamol (400 mg/Kg, v.o.) na água de beber e outro, o grupo controle, foi tratado apenas com água potável. Os animais foram eutanasiados após duas semanas, o sangue foi coletado para análises bioquímicas (ALT, AST, reação de TBARs) e os aneis de traqueias foram isolados e preparados em banho de órgãos para medir a tensão isométrica mediante estímulos contráteis 2+ (curva concentração-efeito para carbacol e KCl; curva concentração-efeito para Ca estimulados com carbacol ou KCl) e relaxantes (isoprenalina, nitroprussiato de sódio e verapamil). Resultados: As enzimas hepáticas ALT, AST e a peroxidação lipídica (TBARs) foram significativamente aumentadas após o tratamento com paracetamol. A capacidade de resposta do músculo liso traqueal das vias aéreas não apresentam qualquer alteração, seja ao estímulo contrátil ou relaxante, como exemplo: agonista 2+ 2+ colinérgico, despolarização da membrana, influxo de Ca pelo sarcolema, liberação interna de Ca do 2+ retículo sarcoplásmico, bloqueio do canal Ca , agonista de receptores β ou relaxamento induzido por doador de NO. Conclusão: O tratamento crônico com paracetamol não induz a hiper ou hiporreatividade das vias aéreas isoladas de ratos.

Submitted by Adriana Martinez (amartinez@unoeste.br) on 2017-05-31T21:00:12Z No. of bitstreams: 1 Fernanda Freire Marin Soares.pdf: 704573 bytes, checksum: bf544d5550ee825719abaa7a01a5e94c (MD5) / Made available in DSpace on 2017-05-31T21:00:12Z (GMT). No. of bitstreams: 1 Fernanda Freire Marin Soares.pdf: 704573 bytes, checksum: bf544d5550ee825719abaa7a01a5e94c (MD5) Previous issue date: 2017-03-20 / Cadmium is a metal that is widely used in industry. Cadmium exposure may result in a variety of pulmonary diseases. No studies have evaluated tracheal damage or even whether cadmium intake can damage the respiratory tract. The aim of this study was to investigate the histopathological changes caused by cadmium poisoning via intake into the respiratory tract and the possible effects of water pH in the genesis of these changes. Ninety male Wistar rats were used and were divided into six groups (n=15): Group A received 400 mg/l cadmium chloride (CdCl2) in the drinking water at a pH of 7.0; group B received CdCl2 (400 mg/l) in the drinking water at a pH of 5.0; group C received CdCl2 (400 mg/l) in the drinking water at a pH of 8.0; group D received water at a pH of 5.0; group E received water at a pH of 8.0; and group F received water at a pH of 7.0. Animals were euthanized after 6 months. Samples of the lung and trachea were removed. The histopathological analysis was performed to evaluate the presence or not of the following parameters: 1. Trachea: inflammatory infiltrate and type of inflammatory cell; tissue congestion; muscle hypertrophy; non-neoplastic lesions of the mucosa; dysplastic lesions; benign and malignant neoplastic lesions; mucus type (acid or basic); and the number of goblet cells; 2. Lung: interstitial inflammatory infiltrate, inflammatory cell type and location; tissue congestion; interstitial fibrosis; emphysema; necrosis of the parenchyma; dysplastic lesions and the presence of benign and malignant neoplastic lesions. Animals exposed to cadmium had a mean of goblet cells in the trachea of 65.83 cells / 6 high-power fields (HPF), while the animals exposed to cadmium had 85.16 cells / 6 HPF (p = 0.012). Pulmonary emphysema occurred in 71.43 to 100% of the cases, while the non-exposed had emphysema in 6.66% to 15.38% of the cases (p <0.001). The respiratory tract is a target for cadmium-related deficits after intake; however, the pH of the water did not influence the development of these lesions. / O cádmio é um metal muito utilizado na indústria. A exposição ao cádmio pode desenvolver uma variedade de doenças pulmonares. Não há na literatura avaliação do dano traqueal ou mesmo se a ingestão de cádmio pode também provocar danos ao trato respiratório. O objetivo do estudo é investigar as alterações histopatológicas causadas por intoxicação por cádmio via ingestão no trato respiratório e os possíveis efeitos do pH da água na gênese destas alterações. Utilizaram-se 90 ratos Wistar, divididos em 6 grupos (n=15): A – solução de cloreto de cádmio (CdCl2 - 400mg/L) na água de beber com pH 7,0; B – CdCl2 (400mg/L) na água de beber com pH 5,0; C – CdCl2 (400mg/L) na água com pH 8,0. D – água com pH 5,0; E – água com pH 8,0; F – água com pH 7,0. Todos os animais foram eutanasiados após 6 meses após o início do experimento. Retiraram-se fragmentos do pulmão e traquéia. A análise histopatológica foi realizada para avaliar presença ou não dos seguintes parâmetros: 1. Traquéia: infiltrado inflamatório e tipo de célula inflamatória; congestão tecidual; hipertrofia da musculatura; lesões não neoplásicas da mucosa; lesões displásicas; lesões neoplásicas benignas e malignas; tipo de muco (ácido ou básico); e o número de células caliciformes; 2. Pulmão: infiltrado inflamatório intersticial, tipo de célula inflamatória e localização; congestão tecidual; fibrose intersticial; enfisema; necrose do parênquima; lesões displásicas e presença de lesões neoplásicas benignas e malignas. Observou-se que os animais expostos ao cádmio apresentarem média de células caliciformes na traquéia de 65,83 células/6 campos de grande aumento (CGA), enquanto que os animais não expostos apresentaram 85,16 células/6CGA (p=0,012). Enfisema pulmonar ocorreu em 71,43 a 100% dos casos, enquanto os não expostos apresentaram enfisema em 6,66 a 15,38% dos casos (p<0,001). Concluiu-se que o trato respiratório é alvo do cádmio também na intoxicação via ingestão, porém o pH da água não influenciou no desenvolvimento das lesões.

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This research was aimed at the development and validation of new in vitro methods capable of predicting in vivo drug deposition from dry powder inhalers, DPIs, in lung-normal human adults. Three physical models of the mouth, throat and upper airways, MT-TB, were designed and validated using the anatomical literature. Small, medium and large versions were constructed to cover approximately 95% of the variation seen in normal adult humans of both genders. The models were housed in an artificial thorax and used for in vitro testing of drug deposition from Budelin Novolizer DPIs using a breath simulator to mimic inhalation profiles reported in clinical trials of deposition from the same inhaler. Testing in the model triplet produced results for in vitro total lung deposition (TLD) consistent with the complete range of drug deposition results reported in vivo. The effect of variables such as in vitro flow rate were also predictive of in vivo deposition. To further assess the method’s robustness, in vitro drug deposition from 5 marketed DPIs was assessed in the “medium” MT-TB model. With the exception of Relenza Diskhaler, mean values for %TLD+SD differed by only < 2% from their literature in vivo. The relationship between inhaler orientation and in vitro regional airway deposition was determined. Aerosol drug deposition was found to depend on the angle at which an inhaler is inserted into the mouth although the results for MT deposition were dependent on both the product and the formulation being delivered. In the clinic, inhalation profiles were collected from 20 healthy inhaler naïve volunteers (10M, 10F) before and after they received formal inhalation training in the use of a DPI. Statistically significant improvements in Peak Inhalation Flow Rate (PIFR) and Inhalation Volume (V) were observed following formalized training. The shapes of the average inhalation profiles recorded in the clinic were found to be comparable to the simulated profiles used in the in vitro deposition studies described above. In conclusion, novel in vitro test methods are described that accurately predict both the average and range of aerosol airway drug deposition seen from DPIs in the clinic.

[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.