Indirect costs of obesity: a review of the current literature.

This study reviews the recent literature on the relationship between obesity and indirect (non-medical) costs. Medline and Web of Science searches were conducted to identify published studies from 1992 to present that report indirect costs by obesity status; 31 studies were included. The indirect costs were grouped into six categories: costs associated with absenteeism, disability, premature mortality, presenteeism, workers' compensation, and total indirect costs. Compared with non-obese workers, obese workers miss more workdays due to illness, injury, or disability. Costs of premature mortality vary substantially across countries. The results for presenteeism and workers' compensation were mixed. More research is needed to determine obesity's causal role in increasing indirect costs, especially for workers' compensation and presenteeism. Cohort and longitudinal study designs should be a priority.

Orally active beta-lactam inhibitors of human leukocyte elastase. 3. Stereospecific synthesis and structure-activity relationships for 3,3-dialkylazetidin-2-ones.

The stereospecific synthesis of several 4-[(4-carboxyphenyl)oxy]- 3,3-dialkyl-1-[[(1-phenylalkyl)-amino]carbonyl]azetidin-2-on es 3 is described in which the C-3 alkyl groups were varied from methyl to butyl as well as allyl, benzyl and methoxymethyl. The structure-activity relations for these compounds are discussed in terms of the hydrolytic stability of the beta-lactam ring, their in vitro inhibitory potency for human leukocyte elastase (HLE), and their in vivo oral efficacy in an HLE-mediated hamster lung hemorrhage assay. Further alkyl substitution on the benzylic urea moiety, especially in the R configuration, afforded enhanced HLE inhibition and in vivo efficacy. The stereochemical assignments for (3R,4S)-4-[(4-carboxyphenyl)oxy]-3-ethyl-3-methyl-1-[[((R)-1- phenylpropyl)amino]carbonyl]azetidin-2-one (42a) (kobs/[I] = 91,000 M-1 s-1) were confirmed with an X-ray structure determination, which was also utilized to develop an HLE inhibition model.

A comparison of alpha 1-proteinase inhibitor methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone and specific beta-lactam inhibitors in an acute model of human polymorphonuclear leukocyte elastase-induced lung hemorrhage in the hamster.

A pharmacokinetic model is described for testing of polymorphonuclear leukocyte (PMN) elastase inhibitors administered by intratracheal or aerosol dosing of hamsters. Acute lung injury, measured as hemorrhage occurring within hours after intratracheal instillation of human PMN elastase, correlated directly with the amount of active enzyme instilled. Hemorrhage began within minutes of elastase instillation, was maximal within 1 h, and remained constant for up to 5 h subsequently. Therefore, inhibition of hemorrhage was used as an assay of the effectiveness of various PMN elastase inhibitors given by the intratracheal route. Lung hemorrhage could also be induced by intratracheal instillation of other elastolytic enzymes, such as thermolysin, and inhibition of hemorrhage was seen only with inhibitors active against the type of elastase used. Methoxysuccinyl-alanyl-alanyl-prolyl-valine-chloromethylketone (MeOSuc-AAPV-CMK), as well as alpha 1-proteinase inhibitor (alpha 1PI) but not tosyl-lysine-chloromethylketone (tosyl-lysine-CMK), inhibited the hemorrhage caused by human PMN elastase, but the specific inhibitors of this enzyme had no effect on thermolysin-induced lung hemorrhage. The duration of activity of these compounds as elastase inhibitors in this model correlated directly with the extent of their persistence in lung lavage fluid as determined by HPLC analysis of compound recovered by bronchoalveolar lavage. (ABSTRACT TRUNCATED AT 250 WORDS)