2 resultados para Parties to actions.
em DigitalCommons@The Texas Medical Center
Resumo:
Childhood obesity is a significant public health problem. Over 15 percent of children in the United States are obese, and about 25 percent of children in Texas are overweight (CDC NHANES). Furthermore, about 30 percent of elementary school aged children in Harris County, Texas are overweight or obese (Children at Risk Institute 2010). In addition to actions such as increasing physical activity, decreasing television watching and video game time, decreasing snacking on low nutrient calorie dense foods and sugar sweetened beverages, children need to consume more fruits and vegetables. According to the National Health and Nutrition Examination Survey (NHANES) from 2002, about 26 percent of U.S. children are meeting the recommendations for daily fruit intake and about 16 percent are meeting the recommendations for daily vegetable intake (CDC NHANES). In 2004, the average total intake of vegetables was 0.9 cups per day and 1.1 cups of fruit per day by children ages four to nine years old in the U.S. (CDC NHANES). Not only do children need effective nutrition education to learn about fruits and vegetables, they also need access and repeated exposure to fruits and vegetables (Anderson 2009, Briefel 2009). Nutrition education interventions that provide a structured, hands-on curriculum such as school gardens have produced significant changes in child fruit and vegetable intake (Blair 2009, McAleese 2007). To prevent childhood obesity from continuing into adolescence and adulthood, effective nutrition education interventions need to be implemented immediately and for the long-term. However, research has shown short-term nutrition education interventions such as summer camps to be effective for significant changes in child fruit and vegetable intake, preferences, and knowledge (Heim 2009). ^ A four week summer camp based on cooking and gardening was implemented at 6 Multi-Service centers in a large, urban city. The participants included children ranging in age from 7 to 14 years old (n=64). The purpose of the camp was to introduce children to their food from the seed to the plate through the utilization of gardening and culinary exercises. The summer camp activities were aimed at increasing the children's exposure, willingness to try, preferences, knowledge, and intake of fruits and vegetables. A survey was given on the first day of camp and again on the last day of camp that measured the pre- and post differences in knowledge, intake, willingness to try, and preferences of fruits and vegetables. The present study examined the short-term effectiveness of a cooking and garden-based nutrition education program on the knowledge, willingness, preferences, and intake among children aged 8 to 13 years old (n=40). The final sample of participants (n=40) was controlled for those who completed pre- and post-test surveys and who were in or above the third grade level. Results showed a statistically significant increase in the reported intake of vegetables and preferences for vegetables, specifically green beans, and fruits. There was also a significant increase in preferences for fruits among boys and participants ages 11 to 13 years. The results showed a change in the expected direction of willingness to try, preferences for vegetables, and intake of fruit, however these were not statistically significant. Interestingly, the results also showed a decrease in the intake of low nutrient calorie dense foods such as sweets and candy.^
Resumo:
Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due to the activation of the transcription factor HSF-1 binding to the promoter region of HSP70 and HSP27 genes. HSF-1 binding subsequently promotes HSP70 and HSP27 gene expression. Based on this, I hypothesized that inhibition of transcription/translation of HSP or client proteins would enhance 17-AAG-mediated cytotoxicity. Multiple myeloma (MM) cell lines MM.1S, RPMI-8226, and U266 were used as a model. To test this hypothesis, two different strategies were used. For the first approach, a transcription inhibitor was combined with 17-AAG. The established transcription inhibitor Actinomycin D (Act D), used in the clinic, intercalates into DNA and blocks RNA elongation. Stress inducible (HSP90á, HSP70 and HSP27) and constitutive (HSP90â and HSC70) mRNA and protein levels were measured using real time RT-PCR and immunoblot assays. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the MM cell lines. This induction of HSP mRNA levels was diminished by 0.05 µg/mL Act D for 12 hours in the combination treatment, except for HSP70. At the protein level, Act D abrogated the 17-AAG-mediated induction of all HSP expression levels, including HSP70. Cytotoxic evaluation (Annexin V/7-AAD assay) of Act D in combination with 17-AAG suggested additive or more than additive interactions. For the second strategy, an agent that affected bioenergy production in addition to targeting transcription and translation was used. Since ATP is necessary for the proper folding and maturation of client proteins by HSP90, ATP depletion should lead to a decrease in client protein levels. The transcription and translation inhibitor 8-Chloro-Adenosine (8-Cl-Ado), currently in clinical trials, is metabolized into its cytotoxic form 8-Cl-ATP causing a parallel decrease of the cellular ATP pool. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the three MM cell lines evaluated. In the combination treatment, 10 µM 8-Cl-Ado for 20 hours did not abrogate the induction of HSP mRNA or protein levels. Since cellular bioenergy is necessary for the stabilization of oncoproteins by HSP90, immunoblot assays analyzing for expression levels of client proteins such as STAT3, Raf-1, and Akt were performed. Immunoblot assays detecting for the phosphorylation status of the translation repressor 4E-BP1, whose activity is modulated by upstream kinases sensitive to changes in ATP levels, were also performed. The hypophosphorylated state of 4E-BP1 leads to translation repression. Data indicated that treatment with 17-AAG alone resulted in a minor (<10%) change in STAT3, Raf-1, and Akt protein levels, while no change was observed for 4E-BP1. The combination treatment resulted in more than 50% decrease of the client protein levels and hypophosphorylation of 4E-BP1 in all MM cell lines. Treatment with 8-Cl-Ado alone resulted in less than 30% decrease in client protein levels as well as a decrease in 4E-BP1 phosphorylation. Cytotoxic evaluation of 8-Cl-Ado in combination with 17-AAG resulted in more than additive cytotoxicity when drugs were combined in a sequential manner. In summary, these data suggest that the mechanism-based combination of agents that target transcription, translation, or decrease cellular bioenergy with 17-AAG results in increase cytotoxicity when compared to the single agents. Such combination strategies may be applied in the clinic since these drugs are established chemotherapeutic agents or currently in clinical trials.