Therefore, we were interested in investigating the PDE4H/PDE4L ratio and suppressive effects of HDME on ovalbumin induced airway hyperresponsive ness, and clarifying its potential for treating asthma and COPD. Although both asthma and COPD are associated with an underlying chronic inflammation of the airways, there are important differences Rapamycin mTOR with regard to the inflammatory cells and mediators involved. The key inflammatory Inhibitors,Modulators,Libraries cells in COPD are macrophages, CD8 T lymphocytes and neutrophils. Macrophages are strongly increased in the airway lumen, lung parench yma and bronchoalveolar lavage fluid. In the airway wall and lung parenchyma, the ratio of CD8 CD4 T lym phocytes increases. Neutrophils are increased in sputum and their number grows with the progression of the dis ease.

In contrast, the key inflammatory cells in asthma are mast cells, eosinophils and CD4 T lymphocytes. Both diseases are sensitive to steroids. However, COPD shows a limited response to inhaled Inhibitors,Modulators,Libraries corticosteroids as compared to the efficacy achieved in asthma. Owing to the side effects of steroids, other therapeutics such as selective PDE4 or dual PDE3/4 inhibitors are develop ing. However, these developing inhibitors are also lim ited for the use of asthma and COPD in clinic because of their emetic side effect. This side effect can be easily assessed in non vomiting species, such as rats or mice, in which selective PDE4 inhibitors reduce the duration of xylazine/ketamine induced anesthesia.

Materials and methods Reagents and animals HDME was synthesized according to a previous method in our laboratory and identified by spectral methods, including ultraviolet, infrared, mass spectroscopy, and nuclear magnetic resonance spectro scopic techniques. The purity of the compound exceeded 98% as determined by high performance liquid chromatography. OVA, methacholine, aluminum Inhibitors,Modulators,Libraries sulfate hexadecahydrate, dimethylsulfoxide, chloralose, urethane, Tris HCl, Bis Tris, benzamidine, fluoride, d,l dithiothrei tol, polyethyleneimine, ethylenediaminetetraacetic acid, Inhibitors,Modulators,Libraries bovine serum albumin, cAMP, cGMP, calmodulin, Dowex resin, Crotalus atrox snake venom, xylazine, and ketamine were purchased from Sigma Chemical. Vinpocetine, erythro 9 adenine HCl, milrinone, 4 2 imidazolidinone, and Zaprinast were purchased from Biomol. Freunds adjuvant was purchased from Pierce Biotechnology.

Mouse Th1/Th2 cytokine CBA kits, and mouse IgE enzyme linked immunosorbent Inhibitors,Modulators,Libraries assay sets were purchased from Pharmingen. Ethyl alcohol and polyethylene glycol 400 were purchased from Merck. cAMP, cGMP, and rolipram were purchased from Amer sham Pharmacia Biotech. Other reagents, such as CaCl2, MgCl2, and NaCl, were of ana lytical grade. HDME and Ro 20 1724 were dissolved in a mixture of ethyl inhibitor Sorafenib alcohol and DMSO. The vehi cle, a mixture of DMSO ethyl alcohol PEG 400 saline used in vivo studies had no abnormal behavior in mice after oral administration. Other reagents were dissolved in distilled water.