Dietary intake, eating behavior, and physical activity-related determinants of high body mass index in rural communities in Wyoming, Montana, and Idaho.

OBJECTIVE: To assess the relation between body mass index (BMI) levels and various lifestyle variables related to physical activity and specific characteristics of a healthy eating pattern, using baseline cross-sectional data from the Wellness IN the Rockies project. SUBJECTS: A total of 928 males and 889 females, aged 18-99 y, recruited from six rural communities in Wyoming, Montana, and Idaho. MEASUREMENTS: Using BMI as the criterion, overweight was defined as a BMI >or=25 kg/m(2) and obesity was defined as a BMI >or=30 kg/m(2). All participants in this study completed a questionnaire that elicited sociodemographic information, self-reported height and weight, and data related to specific dietary intakes, eating-related behaviors, and physical activity behaviors and perceptions. RESULTS: Prevalence of overweight was 70% in men and 59% in women. Increased likelihood of overweight or obesity was associated with greater frequency of the following: drinking sweetened beverages such as soft drinks/soda pop, ordering supersized portions, eating while doing other activities, and watching television. Other predictors were lower frequency of participation in physical activity and the perception of not getting as much exercise as needed. CONCLUSIONS: The increased probability of having a high BMI in individuals who more often eat while doing another activity appears to be a novel finding that will need to be substantiated by additional research. The finding that the vast majority of overweight and obese respondents believed that they do not get as much exercise as needed strengthens the assertion that finding ways to increase participation in physical activity should remain a high priority in obesity prevention and intervention efforts at the community and individual levels.

Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. 1. Selective inhibition of ICAM-1 and E-selectin expression.

A critical early event in the inflammatory cascade is the induced expression of cell adhesion molecules on the lumenal surface of vascular endothelial cells. These adhesion molecules include E-selectin, ICAM-1, and VCAM-1, which serve to recruit circulating leukocytes to the site of the inflammation. These adhesive interactions allow the leukocytes to firmly adhere to and cross the vascular endothelium and migrate to the site of tissue injury. Pharmaceutical agents which would prevent the induced expression of one or more of the cell adhesion molecules on the endothelium might be expected to provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A thieno[2,3-d]pyrimidine, A-155918, was identified from a whole-cell high-throughput assay for compounds which inhibited the tumor necrosis factor-alpha (TNFalpha)-induced expression of E-selectin, ICAM-1, or VCAM-1 on human vascular endothelial cells. Traditional medicinal chemistry methods were applied to this low-micromolar inhibitor, resulting in the 2,4-disubstituted thieno[2,3-c]pyridine A-205804, a potent and selective lead inhibitor of E-selectin and ICAM-1 expression (IC(50) = 20 and 25 nM, respectively). The relative position of the nitrogen atom in the thienopyridine isomer was shown to be critical for activity, as was a small amide 2-substituent.

Synthesis and structure-activity relationships of 2-pyridones: a novel series of potent DNA gyrase inhibitors as antibacterial agents.

Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-alpha]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10-17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis.

Redox glycosidation: the use of Nozaki-Takai methylenylation in a highly stereoselective synthesis of sucrose.

Sequential reaction of 2,3,4,6-tetra-O-benzyl-D-glucopyranose (7) with butyllithium and 2-[2,3,5-tri-O-benzyl-4-O-(tert-butyldiphenylsilyl)-D- arabinonoyl]thio-3-nitropyridine (6) at -78 degrees gave 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl 2,3,5-tri-O-benzyl-4-O-(tert-butyldiphenylsilyl)-D-arabinonate+ ++ (8; 71%, alpha:beta greater than 50:1). Ester carbonyl methylenylation, desilylation, and iodoetherification in the presence of silica gave 3,4,6-tri-O-benzyl-1-deoxy-1-iodo-(2,3,4,6-tetra-O-benzyl-alpha-D- glucopyranosyl)-beta-D-fructofuranoside (15; 44%, alpha:beta greater than 50:1). This neopentylic iodide 15 was converted into sucrose (1;80%) by free-radical substitution using TEMPO (24) followed by sodium-ammonia reduction, acetylation, and Zemplén methanolysis.