Orientador: Ilma Aparecida Paschoal / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-27T12:41:27Z (GMT). No. of bitstreams: 1 Poleti_RosanaGalli_M.pdf: 11378631 bytes, checksum: 23fc2e98ea23383dfc4dfba5668a99a2 (MD5) Previous issue date: 2001 / Resumo: A asma brônquica é largamente conhecida como uma doença inflamatória crônica das vias aéreas e os corticosteróide são as drogas mais efetivas no seu tratamento, pois bloqueiam muitos dos mecanismos inflamatórios e têm ação profilática. Nas últimas décadas, com a introdução da corticoterapia via inalatória, houve redução nos cursos de corticosteróide oral. Porém, existe muita preocupação em relação aos seus efeitos colaterais sistêmicos de impacto clínico, que são: supressão das glândulas supra-renais, osteoporose, catarata, glaucoma, distúrbios metabólicos e, em crianças, retardo do crescimento. O objetivo deste estudo foi avaliar o efeito de dois corticosteróide inalatórios - o dipropionato de beclometasona e o propionato de fluticasona - em doses equivalentes, sobre a resposta das glândulas supra-renais. Vinte pacientes asmáticos participaram do protocolo e foram divididos em dois grupos: o grupo I com o corticosteróide beclometasona na dose de 500 mcg, duas vezes ao dia, e o grupo II com o corticosteróide fluticasona na dose de 250 mcg, duas vezes ao dia. O grupo I foi formado por oito pacientes do sexo feminino e dois pacientes do sexo masculino, com idades entre 18 a 73 anos, todos portadores de asma brônquica de grau leve. O grupo 1 / Abstract: Bronchial asthma is widely known as a chronic inflammatory disease of the airways and corticosteroids are the most effective drugs for asthma treatment since they block many of the inflammatory mechanisms of the disease and they have prophylactic action. In the last decades, with the introduction of inhaled corticotherapy, there was a reduction in the periods of use of oral corticosteroids; although there is concern about its systemic side effects of clinical impact that are: adrenal suppression, osteoporosis, cataracts, glaucoma, metabolic disturbances, in adults; and also growth retard in children. The purpose os this study was the comparison of the effects of two different inhaled corticosteroids - beclomethasone dipropionate and fluticasone propionate ¿ in equivalent doses, over the function of adrenal gland. Twenty asthmatic patients have been divided in two groups: group I treated with beclomethasone in doses of 500 microgram twice a day and group II treated with fluticasone in doses of 250 microgram twice a day. The group I was formed byeight female and two male patients, age varying trom 18 to 73 years, with mild bronchial asthma. Group 11was constituted of six female and four male patients, age varying trom 19 to 67 years; six patients had mild bronchial asthma and four patients had moderate bronchial asthma. After the patients were admitted in the protocol, there was the register of the clinical history and the pulmonary function test, with pre and post bronchodilator studies. After the first dosage of basal cortisol (8:00 am), intravenous injection of cortrosyn was made and new blood samples were collected, 30 and 60 minutes afier the stimulation of adrenal glands. After six months of medication, new blood samples were collected for cortisol dosage at basal conditions, 30 and 60 minutes after stimulation with cortrosyn. The cortisol was measured by the method of chemiluminescence. In relation to the symptoms at the beginning of the protocol, the groups did not show significant differences between them, with the great safeguard that the symptoms have not had graduation of intensity. After six months of medication, the groups also presented similar behaviour; when the comparisonis done in the same group, the patients using fluticasone presented a significant improvement of the dyspnea (p = 0,0233), since seven (70%) of the patients presented dyspnea at the beginning and did not have it in the post medication moment. Nevertheless, it was not the objective of the protocol the evaluation of improvement of the symptoms and the number of patients in each group was too small. The analysis of the pulmonary function tests in the pre and post medication periods shows no significant differences between the groups. It was observed significant improvement of the response to bronchodilator after six months of treatment with both inhaled corticosteroids. The concentration of cortisol, before and after six months of the use of both drugs, did not show alterations in any of the groups. The results of this study show that beclomethasone and fluticasone, at the doses described, used with a spacer attachment, do not cause any detectable adrenal suppression / Mestrado / Clinica Medica / Mestre em Clinica Medica

Orientador: Márcio Alberto Torsoni / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T16:21:53Z (GMT). No. of bitstreams: 1 Pereira_ViniciusDias_M.pdf: 1179657 bytes, checksum: 3d71a3a82020acdf4b2e2a10b8eabfdf (MD5) Previous issue date: 2013 / Resumo: A AMPK hipotalâmica age como um sensor energético e é capaz de modular a ingestão alimentar, homeostase de glicose e a biossíntese de ácidos graxos. É conhecido que a injeção intra-hipotalâmica de ácidos graxos suprime a produção de glicose pelo fígado, principalmente pela ativação de canais de potássio sensíveis a ATP hipotalâmico (K(ATP)). Uma vez que em todos os modelos estudados a biossíntese de malonil-CoA estava envolvida, nós hipotetizamos que a Acetil-CoA Carboxilase poderia modular respostas contra-regulatórias independente da disponibilidade de nutrientes. Nesse estudo foram empregados os seguintes métodos: Immunoblot, PCR em tempo real, ELISA e avaliações bioquímicas. Através desses métodos, nós mostramos que a redução da expressão de acetil-CoA carboxilase pela injeção de oligonucleotídeo antisense intraventricular resultou no aumento da ingestão alimentar e diminuiu a expressão dos mRNA de CART, CRH e TRH. Além disso, como nos ratos em jejum, os ratos tratados com oligonucleotídeo antisense apresentaram concentrações de corpos cetônicos e glucagon séricos aumentados, além de níveis de insulina e glicogênio hepático diminuídos. A redução de acetil-CoA carboxilase hipotalâmica também aumentou a expressão de PEPCK, fosforilação de AMPK e a produção de glicose no fígado. Interessantemente, esses efeitos foram observados sem modificação da fosforilação da AMPK hipotalâmica. Com isso, concluímos que a inibição da ACC hipotalâmica pode ativar resposta contra-regulatória hepática independente da ativação da AMPK hipotalâmica / Abstract: BACKGROUND: Hypothalamic AMPK acts as a cell energy sensor and can modulate food intake, glucose homeostasis, and fatty acid biosynthesis. Intrahypothalamic fatty acid injection is known to suppress liver glucose production, mainly by activation of hypothalamic ATP-sensitive potassium (K(ATP)) channels. Since all models employed seem to involve malonyl-CoA biosynthesis, we hypothesized that acetyl-CoA carboxylase can modulate the counter-regulatory response independent of nutrient availability. METHODOLOGY/PRINCIPAL FINDINGS: In this study employing immunoblot, realtime PCR, ELISA, and biochemical measurements, we showed that reduction of the hypothalamic expression of acetyl-CoA carboxylase by antisense oligonucleotide after intraventricular injection increased food intake and diminished the expression of CART, CRH, and TRH mRNA. Additionally, as in fasted rats antisense oligonucleotide-treated rats, increased serum glucagon and ketone bodies were observed along with diminished levels of serum insulin and hepatic glycogen. The reduction of hypothalamic acetyl-CoA carboxylase also increased PEPCK expression, AMPK phosphorylation, and glucose production. Interestingly, these effects were observed without modification of hypothalamic AMPK phosphorylation. CONCLUSION/SIGNIFICANCE: Hypothalamic ACC inhibition can activate hepatic counter-regulatory response independent of hypothalamic AMPK activation / Mestrado / Clinica Medica / Mestre em Clinica Medica