We conclude that stabilization of exogenous surfactant by adding imipramine to create a "fortified surfactant preparation" improves lung function in a clinically relevant piglet model, and that this effect can be attributed to the inhibition of a-SMase as evidenced in the mouse model.
A series of multifunctional (chloromethyl)silanes have been synthesized: Cl 2 Si(CH 2 Cl) 2 (1), (MeO) 2 Si(CH 2 Cl) 2 (2), tris(chloromethyl)(2,4,6-trimethoxyphenyl)silane (3), ClSi(CH 2 -Cl) 3 (4), MeOSi(CH 2 Cl) 3 (5), Si(CH 2 Cl) 4 ( 6), and ClCH 2 CH 2 Si(CH 2 Cl) 3 ( 7). The synthesis of these compounds is based on coupling reactions between (chloromethyl)lithium, generated in situ from bromochloromethane and n-butyllithium in tetrahydrofuran, and chlorosilanes. Compounds 1-7 were characterized by NMR studies ( 1 H, 13 C, 29 Si) and elemental analyses, and 3 and 6 were additionally studied by single-crystal X-ray diffraction. Silanes with more than one SiCH 2 Cl moiety and compounds of this type with additional Si-functional groups are of great interest for synthetic organosilicon chemistry.
Supplementation of exogenous surfactant with a NF-[kappa]B inhibitor to create a "fortified" surfactant improves gas exchange, lung function, and pulmonary edema during 24 hrs of mechanical ventilation, without a secondary functional relapse. Inhibition of NF-[kappa]B suppressed acid sphingomyelinase activity and ceramide generation, indicating a novel proinflammatory link of NF-[kappa]B.
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