Browsing by Author "Namuduri, Anuradha"
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Item INHIBITION OF HYPOXIA INDUCIBLE FACTOR 1A BY SOY PHYTOESTROGENS: A POTENTIAL MECHANISM FOR NEUROPROTECTION IN STROKE(2013-04-12) Namuduri, AnuradhaPurpose: Despite a multitude of endogenous mechanisms to compensate for transient decreases in glucose and oxygen delivery to the brain, ischemic stroke remains the third leading cause of death and the leading cause of long-term disability in the United States. Studies in animal models of cerebral ischemia have shown that both endogenous and exogenous estrogens improve histological and behavioral stroke outcomes. Similarly, phytoestrogens derived from soy and other plant products can reduce stroke injury in the lab. These compounds are structurally similar to estrogen and bind to and activate estrogen receptors. Our overall hypothesis is that soy phytoestrogens can induce adaptive responses in the brain to favor increased survival and cell repair. One early adaptive response to ischemia is activation of the oxygen homeostasis mediator hypoxia-inducible factor 1 alpha (HIF-1 alpha), a normally labile protein that is stable under conditions of low oxygen. Despite the importance of HIF-1 alpha in the adaptive response to hypoxia and ischemia, acute overactivation of this protein increases cerebral edema and cell death. The purpose of this research is to determine if soy phytoestrogens (genistein, daidzein, equol) inhibit acute ischemic injury by attenuating the detrimental actions of HIF-1 alpha. Methods: In vitro, HT22 hippocampal cells were treated with 0.1 or 1 micromolar genistein and exposed to oxygen and glucose deprivation to mimic conditions of ischemia within the brain. In vivo, ovariectomized female Sprague Dawley rats were fed a soy-free or high soy diet for 4 weeks followed by 90 minutes experimental stroke and 4-24 hours of recovery. HIF-1 alpha levels were determined by Western blotting for the HIF-1 alpha targets vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and BCL2/adenovirus E1B 19kDa interacting protein 3 (BNIP3). Results: In HT22 cells, genistein attenuated the HIF-1 alpha response to ischemia and increased degradation of HIF-1 alpha. Rats fed a high soy diet had significantly decreased levels of HIF-1 alpha and it's targets VEGF, eNOS, and BNIP3 in the ischemic hemisphere compared to rats on a soy-free diet. Conclusions: These results suggest that one mechanism of phytoestrogen neuroprotection is the attenuation of acute detrimental effects of HIF-1 alpha. These results further support the potential for dietary phytoestrogens as an effective prophylactic step in the prevention and management of ischemic strokes.Item Internalizing Behaviors in Hispanic Boys Predict Overweight/Obese Status(2016-03-23) Franks, Susan; Fulda, Kimberly; Habiba, Nusrath; Namuduri, AnuradhaBackground: Obesity has been a troubling trend among Hispanic youth. Emotional eating has been described as the consumption of comfort food to cope with negative emotions, which in turn can contribute to weight gain. Negative emotions can lead to internalizing (feeling worthless, sad, withdrawn) and externalizing (bullying, arguing, disobeying, stubbornness) behaviors. Studies suggest these may precede obesity in children with poor socioeconomic status. The aim of this study was to examine these behaviors in relation to weight in under served Hispanic children. Hypotheses: Overweight children (OW) will have higher internalizing or externalizing behaviors as compared to normal weight children (NW). Methods: Subjects included Hispanic youths (117 males, 116 females) ages 10-14. Subjects were classified into NW (n=85) and OW (n=148) based on BMI percentile. Parents completed a 1-5 Likert scale survey of social-emotional behaviors. Responses were summed to arrive at scores for Internalizing (INT) and Externalizing (EXT) behaviors. Relationships between INT, EXT, age, and BMI percentile were examined for boys and girls separately using Spearman correlation. Logistic regressions were conducted to ascertain the effects of significantly associated variables on the likelihood that subjects would be OW. Results: For boys, BMI percentile was associated with INT (rs=.180, p=.053) and age (rs=.215, p=.020). Girls showed no significant correlations. Logistic regression for boys using INT and age was significant (X2=10.570, p=.005). Increasing age in boys was significantly associated with an increased likelihood of being OW (OR= 1.439, CI=1.056 – 1.961). The Wald criterion indicated that increases in INT approached significance in predicting OW (p=.069). EXT was not significant for boys. Regression models for girls were not significant. Conclusion: Internalizing behaviors increased for boys who were overweight or obese, especially with increasing age. This trend was not significant in girls. These data contradict previous literature suggesting Hispanic girls are at higher risk for obesity due to increased internalizing behaviors. Future research should broaden the scope of internalizing behaviors that may place children at risk for obesity. Acknowledgments: This study was supported by intramural grants, and the study was approved by the IRB at the University of North Texas Health Science Center.