Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-02-13T10:28:30Z No. of bitstreams: 2 Tese - Ana Paula Araújo Costa - 2016.pdf: 2728666 bytes, checksum: 2cd43bd911125e81ab1a9483baff4302 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-02-13T10:29:52Z (GMT) No. of bitstreams: 2 Tese - Ana Paula Araújo Costa - 2016.pdf: 2728666 bytes, checksum: 2cd43bd911125e81ab1a9483baff4302 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-02-13T10:29:52Z (GMT). No. of bitstreams: 2 Tese - Ana Paula Araújo Costa - 2016.pdf: 2728666 bytes, checksum: 2cd43bd911125e81ab1a9483baff4302 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-12-16 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Dilated cardiomyopathy (DCM) is a disease of the heart muscle that culminates in dilatation of the left ventricle, or both, and myocardial contractile dysfunction. The clinical phase of the disease is characterized by congestive heart failure signs (CHF), with or without arrhythmias. The treatment involves the use of drugs aimed at reducing the signs of CHF and arrhythmias, with diuretics, positive inotropic, vasodilator and antiarrhythmic. A new drug candidate (LASSBio 294), capable of promoting combined positive inotropic and vasodilating effects, has recently been developed, and have been tested in pre-clinical study in healthy Beagle dogs with promising results. Therefore, this study proposed to verify the action of the drug prototype LASSBio 294, at a dose of 2mg/Kg on cardiovascular parameters of rabbits with DCM experimentally induced by doxorubicin, using as positive control the pimobendan at a dose of 0.3mg/kg. The DCM was induced by intravenous administration of 1 mg/kg of doxorubicin, at a concentration of 2mg/ml, twice a week, for three weeks, and then weekly until it reached fractional shortening less or equal to 25%. As methods of evaluating the LASSBio 294 action on the cardiovascular system of rabbits and monitor the induction of DMC, the following tests were performed: electrocardiography, echodopplercardiography, measurement of blood pressure, chest radiograph, dosage of cardiac lesions, and kidney and liver function biomarkers and hematologic evaluation. At the end of the induction protocol the animals were randomly divided into two groups A (LASSBio 294) and B (pimobendan) and underwent treatment for 30 days, twice a day. At the end of the study it was concluded that the DCM model induced by doxorubicin is a good model to study the disease and its consequences, leading to systolic and diastolic dysfunction with dilatation of the left ventricle. However the time for induction of DCM is inaccurate and the occurrence of multisystemic toxicity, such as nephrotoxicity and myelosuppression, contributes to high mortality rate in this model (35%). It can be concluded that LASSBio 294 is effective in increasing systolic function, improving diastolic function, without altering rabbits blood pressure, has no pro-arrhythmogenic or toxic effect, and reduced the serum creatinine concentration of the animals, but it does not prevent the evolution of the congestive condition. / A cardiomiopatia dilatada (CMD) é uma enfermidade do músculo cardíaco que culmina em dilatação do ventrículo esquerdo, e/ou direito, e disfunção contrátil do miocárdio, sendo a fase clínica da doença caracterizada por sinais de insuficiência cardíaca congestiva (ICC), com ou sem a presença de arritmias. O tratamento envolve a utilização de fármacos que visem diminuir os sinais de ICC e as arritmias, sendo os diuréticos, inotrópicos positivos, vasodilatadores e antiarrítmicos os mais utilizados. Recentemente foi desenvolvido um novo candidato a fármaco (LASSBio 294) capaz de promover os efeitos vasodilatador e inotrópico positivo combinados, tendo sido testado em estudo pré-clínico em cães saudáveis da raça Beagle, com resultados promissores. Propôs-se neste estudo verificar a ação do protótipo a fármaco LASSBio 294, na dose de 2mg/kg, sobre os parâmetros cardiovasculares de coelhos com CMD experimentalmente induzida por doxorrubicina, utilizando como controle positivo o tratamento com a pimobendana, na dose de 0,3mg/Kg. A CMD foi induzida por meio da administração endovenosa de 1mg/Kg de doxorrubicina, na concentração de 2mg/mL, duas vezes na semana, por três semanas e depois semanalmente até que alcançada fração de encurtamento igual ou inferior a 25%. Como métodos de avaliação da ação do LASSBio 294 sobre o sistema cardiovascular de coelhos e monitoramento da indução da CMD, foram realizados os seguintes exames: eletrocardiografia, ecodopplercardiografia, mensuração da pressão arterial, radiografia torácica, dosagem de biomarcadores de lesão cardíaca, de função renal e hepática e avaliação hematológica. Ao final do protocolo de indução os animais foram distribuídos aleatoriamente em dois grupos, A (LASSBio 294) e B (pimobendana), e foram submetidos a tratamento durante trinta dias, duas vezes ao dia. Ao final do estudo foi possível concluir que o modelo de CMD induzida por doxorrubicina é um bom modelo para estudo da doença e suas consequências, induzindo disfunção sistólica e diastólica do miocárdico, com dilatação do ventrículo esquerdo. Porém, o tempo para indução da CMD é inexato e a ocorrência de toxicidade multissistêmica, como a mielossupressão e nefrotoxicidade, contribui para a elevada taxa de mortalidade dos animais (35%). Ainda, conclui-se que o LASSBio 294 é eficiente em incrementar a função sistólica, melhorar a função diastólica, sem alterar a pressão arterial dos coelhos, não apresentando efeito pró arritmogênico ou tóxico, e reduzindo a concentração sérica de creatinina dos animais, porém não impede a evolução do quadro congestivo.

Combination corticosteroid inhalers are the primary treatment option for long-term pulmonary disorders including asthma, persistent bronchitis, and chronic obstructive pulmonary disease. Common side effects of these medications are xerostomia in the mouth and throat, hoarseness, and soreness in the oropharynx. Research indicates that a large percentage of the inhaler particles are deposited onto laryngeal tissue, leaving an alteration of laryngeal mucosal properties. As the first stage in a long-term project, this thesis addresses the need for baseline phonatory data that will lay groundwork for quantifying inhaler-induced phonatory changes. Excised larynx research is a powerful tool for assessing aerodynamic alterations that accompany laryngeal pathology. Porcine (pig) larynges are a traditional species employed in voice disorder research, though leporine (rabbit) larynges are an emerging species that lends itself to histologic vocal fold studies as they have the most similar vocal fold cover structure to humans compared to any other animal to date. The purpose of this study was to examine the measurement stability of six aerodynamic parameters in a traditional excised larynx benchtop model. Specifically, the current author assessed measurement stability of leporine larynges compared to porcine larynges with the following aerodynamic metrics: phonation onset pressure (PTP; cmH2O), phonation onset flow (PTF; L/m), sustained pressure (cmH2O), sustained flow (L/m), onset laryngeal resistance (cmH2O/L/m), and sustained laryngeal resistance (cmH2O/L/m). A total of 30 larynges—15 leporine and 15 porcine—were mounted on a benchtop setup; phonation was sampled over 15 trials for each larynx. Measurement stability for the above six tokens was examined using coefficient of variation (%) analyses. Leporine larynges demonstrated significantly less variation across all six aerodynamic parameters when compared to porcine larynges. The leporine PTP values were most stable as compared to leporine and porcine pressure and airflow values. Leporine airflow values were also more stable than porcine PTP and PTF values. These results indicate that leporine larynges might be a preferred excised larynx specimen for certain benchtop phonation studies. These findings are important for establishing expected measurement variability in porcine and leporine larynges, particularly when translating benchtop research to laryngeal pathology.