Thesis (doctoral)--University of Lund, 1995. / Added t.p. with thesis statement inserted.

Thesis (Ph.D.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

Músculos esqueléticos de ratos idosos apresentam uma reduzida capacidade de se regenerar após lesão. No presente estudo, nós lançamos a hipótese de que a estimulação farmacológica de adrenoceptores b2 em músculos de ratos idosos lesados poderia melhorar a regeneração destes. Ratos jovens e idosos foram tratados com injeção subcutânea do agonista b2-adrenérgico formoterol (2 mg/kg/dia) durante 10 e 21 dias após lesão do músculo sóleo. Os músculos de ratos idosos lesados e tratados com formoterol por 10 e 21 dias apresentaram menor processo inflamatório e fibras musculares em regeneração com maior calibre quando comparados aos músculos apenas lesados. O tratamento com formoterol preveniu a queda da força tetânica e aumentou a síntese de proteínas e a fosforilação de mTOR em músculos de ratos idosos lesados e avaliados após 10 dias. Nossos resultados sugerem que o formoterol melhora a capacidade regenerativa estrutural e funcional dos músculos esqueléticos de ratos idosos, e que esse efeito é mediado pelo aumento da síntese protéica através da ativação de mTOR. / Skeletal muscles from old rats fail to completely regenerate following injury. In the present work, we hypothesized that pharmacological stimulation of b2-adrenoceptors in aged muscles following injury could improve their regenerative capacity. Young and aged rats were treated with a subcutaneous injection of b2-adrenergic agonist formoterol (2 mg/kg/day) up to 10 and 21 days after soleus muscle injury. Formoterol-treated muscles from old rats evaluated at 10 and 21 days post-injury showed reduced inflammation and regenerating myofibers of greater caliber when compared to their injured controls. Formoterol minimized the decrease in tetanic force and increased protein synthesis and mTOR phosphorylation in old muscles at 10 days post-injury. Our results suggest that formoterol improves structural and functional regenerative capacity of regenerating skeletal muscles from aged rats by increasing protein synthesis via mTOR activation.

This thesis records a series of experiments conducted to gain further insight into factors which influence the expression, ligand binding and functional activity of the beta-2 adrenergic receptor. These studies were prompted by previous reports that the postulated beta-2 adrenergic receptor abnormality in allergic asthma could be induced, induced by autoantibodies. I established and optimised beta-2 adrenergic receptor ligand binding and functional assays in guinea pig lung membranes and then conducted an original study of beta adrenergic receptor expression in the guinea pig foetal lung. I found that beta adrenergic receptor expression in the foetal lung was dormant for 80% of the gestation period. After day 53 there was a surge in receptor expression which increased beyond term.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24133号 / 医博第4873号 / 新制||医||1059(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 生田 宏一, 教授 濵﨑 洋子, 教授 森信 暁雄 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

No description available.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / Anaesthesiology / Master / Master of Philosophy

The premature infant is subject to pathological alterations of the cardiovascular system leading to insufficient pulmonary blood flow and/or sudden surges of pressure to fragile cerebral blood vessels, conditions which are often associated with hypotension. Dobutamine appears to be a potentially useful agent to increase pulmonary blood flow and correct hypotension. In view of this potential, the alpha-adrenergic characteristics of dobutamine acts were studied in the isolated rabbit femoral and pulmonary arteries. Dobutamine on the post synaptic membrane of these tissues as a high affinity, low intrinsic activity alpha adrenergic agonist. No action of dobutamine to modulate stimulation evoked release of norepinephrine was found, although dobutamine did increase spontaneous release of norepinephrine. This effect was not blocked by antagonists of uptake 1 and uptake 2. To further evaluate dobutamine for use in the neonate, contractile responses of the femoral and pulmonary arteries and aorta to dobutamine and norepinephrine were studied in dogs of various ages from newborn to 6 weeks. Maximal contractile responses to norepinephrine in the pulmonary artery and aorta increased with age. Dobutamine produced small or no responses in all newborn tissues studied and also showed increasing responsiveness with age. To allow future study of the mechanism of these changes a method of radioligand binding was established for vascular smooth muscle using the ligands prazosin and rauwolscine in the dog and rabbit pulmonary artery and aorta. This binding was found to demonstrate the properties of saturability, sterospecificity and rank order of potency. Possible variables that could account for the observed changes in response during maturation were mathematically modeled to provide a theoretical basis for future studies combining measurement of contractile response and radioligand binding techniques.