Therapeutic Effect of Rapamycin on Aortic Dissection in Mice.

Aortic dissection (AD) is a serious clinical condition that is unpredictable and frequently results in fatal outcome. Although rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has been reported to be effective in preventing aortopathies in mouse models, its mode of action has yet to be clarified. A mouse AD model that was created by the simultaneous administration of ß-aminopropionitrile (BAPN) and angiotensin II (AngII) for 14 days. Rapamycin treatment was started either at day 1 or at day 7 of BAPN+AngII challenge, and continued throughout the observational period. Rapamycin was effective both in preventing AD development and in suppressing AD progression. On the other hand, gefitinib, an inhibitor of growth factor signaling, did not show such a beneficial effect, even though both rapamycin and gefitinib suppressed cell cycle activation in AD. Rapamycin suppressed cell cycle-related genes and induced muscle development-related genes in an AD-related gene expression network without a major impact on inflammation-related genes. Rapamycin augmented the activation of Akt1, Akt2, and Stat3, and maintained the contractile phenotype of aortic smooth muscle cells. These findings indicate that rapamycin was effective both in preventing the development and in suppressing the progression of AD, indicating the importance of the mTOR pathway in AD pathogenesis.

Lessons from the 2006 Louisiana health and population survey.

The 2005 hurricane season caused extensive damage and induced a mass migration of approximately 1.1 million people from southern Louisiana in the United States. Current and accurate estimates of population size and demographics and an assessment of the critical needs for public services were required to guide recovery efforts. Since forecasts using pre-hurricane data may produce inaccurate estimates of the post-hurricane population, a household survey in 18 hurricane-affected parishes was conducted to provide timely and credible information on the size of these populations, their demographics and their condition. This paper describes the methods used, the challenges encountered, and the key factors for successful implementation. This post-disaster survey was unique because it identified the needs of the people in the affected parishes and quantified the number of people with these needs. Consequently, this survey established new population and health indicator baselines that otherwise would have not been available to guide the relief and recovery efforts in southern Louisiana.

Synthesis of trans-fused tetrahydrooxepins: stereoselective allylation of sulfur or fluoro-substituted tetrahydrooxepins.

An efficient route to the trans-fused tetrahydrooxepin corresponding to the E ring of ciguatoxin was developed. Wide screening of allylation reactions of sulfur or fluoro-substituted tetrahydrooxepin revealed that the optimum method for obtaining the beta-allylation product selectively was the use of a combination of allyltrimethylsilane and TiCl(4) with 6-fluoro-7-hydroxytetrahydrooxepin.

Formal total synthesis of neocarzinostatin chromophore.

[reaction: see text] An efficient route to the neocarzinostatin chromophore aglycon has been developed. The present strategy involves a stereoselective intramolecular acetylide-aldehyde cyclization to form the C5-C6 bond, followed by efficient installation of alpha-epoxide, naphthoate, and carbonate functionalities. The C8-C9-olefin was introduced by using the Martin sulfurane dehydration reaction to furnish the highly reactive aglycon.