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14 27 Hypothyroidism minimizes experimental autoimmune myocarditis in rats Zhi-ping Zong and Shinobu Matsui Medical Res. Inst., Kanazawa Medical University It has been well known that thyroid hormone is essential for normal growth and development of almost all organ systems and has profound effects on the heart and circulation. However, little is known about the effect of thyroid hormone on myocarditis. In the present study, we demonstrate that hypothyroidism minimized and hyperthyroidism potentiated experimentally autoimmune myocarditis (EAM) in rats. [Methods] Rats suffering from EAM were divided into 3 groups. In detail, 1) Euthyroidism group: saline injection, 2) Hypothyroidism group: p.o. of methimazole, and 3) Hyperthyroidism group: i.p. injection of triiodothyronine. [Results] Histologically, 1) Euthyroidism group: multifocal infiltration of inflammatory cells mainly consisting of lymphocytes, 2) Hypothyroidism group: mild infiltration, and 3) Hyperthyroidism group: severe infiltration. [Conclusion] The findings of our stydies suggest that decreased thyroid function may be beneficial for the insulted myocardia. Possible application of these results to humans merits evaluation in clinical trials.

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24 48 Recombinant Sendai Virus Can Overcome Biological Barriers to Current Airway Gene Transfer Vectors Clinical studies of gene therapy for cystic fibrosis (CF) suggest that the efficiency of gene transfer to the airway epithelium needs to be improved. Recent laboratory studies suggested that some biological barriers, such as airway mucus and tight junctions on apical well differentiated airway cells, reduce gene transfer efficiencies of lipid-and adenovirus-mediated gene transfer. We have recently developed a novel gene transfer ageant, recombinant Sendai virus (SeV), and in this study have assessed it for gene transfer to native airway epithelium. We show that SeV produces efficient transfection throughout the respiratory tract of both mice and ferret in vivo, and gene transfer efficiency was estimated more than 80 % of bronchial epithelial cells in both models. Interestingly, several % of submucosal glandular epithelial cells also expressed foreign gene. SeV also efficiently transfected freshly obtained human nasal epithelium. This effect was not inhibited by the presence of mucus in an ex vivo sheep airway model, while lipid-mediated gene transfer was reduced approximately 25-fold by mucus. In addition, this model system also showed that efficient luciferase and EGFP gene transfer not only to injured edges but also to uninjred apical surface of tracheal tissue, while recombinant adenoviruses could transfect efficiently only to injured edges of the mucosa. In these four model systems, SeV produced gene transfer efficiency which was several log orders greater magnitude than found with adenovirus or cationic liposomes, and may provide an important new vector for airway gene transfer.

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