ABSTRACT
One factor contributing to the childhood obesity epidemic is easy access to foods with high fat content available in public schools. After several years of advocacy efforts conducted by a city-wide coalition, the public schools system in an urban Midwestern city introduced fresh salad bars for lunch in three schools. Researchers have argued, however, that the introduction of salad bars in schools, without nutrition education, is not enough to produce changes in eating patterns. In this study, researchers used a target and control school to evaluate the impact of a 5-month nutrition education program. The results indicated that once the nutrition education program was implemented, the number of children consuming salad entrees and salad items doubled and quadrupled respectively, and knowledge about fruits and vegetables increased. Implications for community researchers interested in addressing childhood obesity are discussed.
Subject(s)
Community-Institutional Relations , Health Education/organization & administration , Health Promotion/organization & administration , Pediatric Obesity/prevention & control , Urban Population/statistics & numerical data , Child , Community-Based Participatory Research , Humans , Lunch , Pediatric Obesity/epidemiology , United States/epidemiologyABSTRACT
Cathepsin L is a cysteine protease that is upregulated in a variety of malignant tumors and plays a significant role in cancer cell invasion and migration. It is an attractive target for the development of small-molecule inhibitors, which may prove beneficial as treatment agents to limit or arrest cancer metastasis. We have previously identified a structurally diverse series of thiosemicarbazone-based inhibitors that incorporate the benzophenone and thiochromanone molecular scaffolds. Herein we report an important extension of this work designed to explore fused aryl-alkyl ring molecular systems that feature nitrogen atom incorporation (dihydroquinoline-based) and carbon atom exclusivity (tetrahydronaphthalene-based). In addition, analogues that contain oxygen (chromanone-based), sulfur (thiochroman-based), sulfoxide, and sulfone functionalization have been prepared in order to further investigate the structure-activity relationship aspects associated with these compounds and their ability to inhibit cathepsins L and B. From this small-library of 30 compounds, five were found to be strongly inhibitory (IC50 <500 nM) against cathepsin L with the most active compound (7-bromodihydroquinoline thiosemicarbazone 48) demonstrating an IC50=164 nM. All of the compounds evaluated were inactive (IC50 >10,000 nM) as inhibitors of cathepsin B, thus establishing a high degree (>20-fold) of selectivity (cathepsin L vs. cathepsin B) for the most active cathepsin L inhibitors in this series.
Subject(s)
Cathepsin L/antagonists & inhibitors , Protease Inhibitors/chemistry , Small Molecule Libraries/chemistry , Cathepsin B/antagonists & inhibitors , Cathepsin B/metabolism , Cathepsin L/metabolism , Chromans/chemistry , Protease Inhibitors/chemical synthesis , Protease Inhibitors/metabolism , Protein Binding , Quinolines/chemistry , Safrole/analogs & derivatives , Safrole/chemistry , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/metabolism , Structure-Activity Relationship , Sulfones/chemistry , Tetrahydronaphthalenes/chemistryABSTRACT
A series of 36 thiosemicarbazone analogues containing the thiochromanone molecular scaffold functionalized primarily at the C-6 position were prepared by chemical synthesis and evaluated as inhibitors of cathepsins L and B. The most promising inhibitors from this group are selective for cathepsin L and demonstrate IC50 values in the low nanomolar range. In nearly all cases, the thiochromanone sulfide analogues show superior inhibition of cathepsin L as compared to their corresponding thiochromanone sulfone derivatives. Without exception, the compounds evaluated were inactive (IC50 > 10000 nM) against cathepsin B. The most potent inhibitor (IC50 = 46 nM) of cathepsin L proved to be the 6,7-difluoro analogue 4. This small library of compounds significantly expands the structure-activity relationship known for small molecule, nonpeptidic inhibitors of cathepsin L.
ABSTRACT
Antimicrobial agent usage is common in animal agriculture for therapeutic and prophylactic purposes. Selective pressure exerted by these antimicrobials on soil bacteria could result in the selection of strains that are resistant due to chromosomal- or plasmid-derived genetic components. Multiple antimicrobial resistances in Escherichia coli and the direct relationship between antimicrobial agent use over time has been extensively studied, yet the relationship between the age of an animal agriculture environment such as a dairy farm and antibiotic resistance remains unclear. Therefore, we tested the hypothesis that antimicrobial-resistance profiles of E. coli isolated from dairy farm topsoil correlate with dairy farm age. E. coli isolated from eleven dairy farms of varying ages within Roosevelt County, NM were used for MIC determinations to chloramphenicol, nalidixic acid, penicillin, tetracycline, ampicillin, amoxicillin/clavulanic acid, gentamicin, trimethoprim/sulfamethoxazole, cefotaxime, and ciprofloxacin. The minimum inhibitory concentration values of four antibiotics ranged 0.75 to >256 µg/ml, 1 to >256 µg/ml, 12 to >256 µg/ml, and 0.75 to >256 µg/ml for chloramphenicol, nalidixic acid, penicillin, and tetracycline, respectively. The study did not show a direct relationship between antibiotic resistance and the age of dairy farms.
