Matching Items (63)

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Genistein-mediated diet tends to increase oxidative stress in the vasculature of female ob/ob mice

Description

Morbid obesity is associated with cardiovascular and metabolic disorders. A major contributor to the pathogenesis of these diseases is impaired vasodilation resulting from elevated reactive oxygen species (ROS). This is

Morbid obesity is associated with cardiovascular and metabolic disorders. A major contributor to the pathogenesis of these diseases is impaired vasodilation resulting from elevated reactive oxygen species (ROS). This is because certain ROS such as superoxide are raised with obesity and scavenge the endogenous vasorelaxant nitric oxide, resulting in hypertension. The objective of this study was to measure the ability of genistein to quench superoxide in the vasculature of ob/ob mice, an animal model of obesity and type 2 diabetes. Genistein is an isoflavonic phytoestrogen naturally found in soy products. While genistein has documented antioxidant and anti-inflammatory properties, it is not known whether this protects the vasculature from oxidative stress. Genistein was hypothesized to reduce superoxide in arteries from female ob/ob mice. The superoxide indicator dihydroethidium (DHE) [2µL/mL HEPES buffer] was added to isolated aortae and mesenteric arteries from mice fed either a control (standard rodent chow containing 200-300 mg genistein/kg) or genistein-enriched (600mg genistein/kg rodent chow) diets for 4 weeks. Frozen tissues sections were collected onto glass microscope slides and examined using confocal microscopy. Contrary to the hypothesis, a diet containing twice the amount of genistein found in standard chow did not significantly reduce superoxide concentrations in aortae (p=0.287) or mesenteric arteries (p=0.352). Superoxide dismutase, an antioxidant enzyme that breaks down superoxide, was significantly upregulated in the genistein-enriched diet group (p=0.004), although this elevation did not promote the breakdown of superoxide. In addition, the inflammatory marker iNOS was not downregulated in the genistein-enriched diet group (p>0.05). The results indicate that high amounts of isoflavones, like genistein, may not exhibit the purported antioxidant effects in the vasculature of obese or diabetic subjects. Further studies examining arteries from ob/ob mice fed a genistein-free diet are needed to elucidate the true effects of genistein on oxidative stress.

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  • 2014-05

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Differential Activation of Unfolded Protein Response in Two Osteosarcoma Cell Lines Following Hypoxic and Chemotherapeutic Stress

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Osteosarcoma (OS) is the most prevalent primary tumor of bone in the pediatric age group [1]. The long-term cancer free survival has improved in patients with localized cancer; however, less

Osteosarcoma (OS) is the most prevalent primary tumor of bone in the pediatric age group [1]. The long-term cancer free survival has improved in patients with localized cancer; however, less than 20% of patients diagnosed with metastatic disease survive without relapse [2]. While these findings emphasize the urgent need for new therapeutic agents, the lack of understanding of the factors and the tumor microenvironment that lead to therapy resistance in OS has significantly hampered progress towards improved prognosis. Recent clinical reports have shown a negative correlation between tumor hypoxia and overall survival in OS patients [4]. In addition to the up-regulation of hypoxia inducible factors (HIFs), it has been shown that hypoxia can trigger an adaptive response such as the unfolded protein response (UPR) that allows tumor cells to avoid therapy-induced death [3,4,7,10].
Using in vitro experimental models of both SAOS-2 (non-metastatic) and 143-b (metastatic) osteosarcoma cell lines and Western blot analysis, we have demonstrated that basal levels of molecular chaperone BiP (Binding immunoglobulin protein, or GRP-78) and peIF2α (phospho-eukaryotic initiation factor 2 alpha), both markers of the UPR, were higher in SAOS-2 than 143-b cells. We also show that both these markers were further up-regulated upon exposure to hypoxia, as evidenced by the increase in banding intensity in both SAOS-2 and 143-b cells. Furthermore, analysis of another UPR marker, ATF6 (activating transcription factor 6) showed that basal levels of active nuclear ATF6 were slightly higher in SAOS-2 cells than in 143-b cells. However, unlike the other UPR markers these levels were significantly reduced upon exposure to hypoxia (0.1% O2). In addition to hypoxia, treatment with Cisplatin also had similar effects on the expression of aforementioned UPR markers: BiP and peIF2α. We found that the 143-b OS cells were more sensitive to the Cisplatin treatment than the SAOS-2 OS cells, and thus more prone to cell-mediated death.
Our findings shed light on the unknown mechanisms underlying chemotherapeutic drug resistance in osteosarcoma patients. Our research may lead to novel therapies that seek out and destroy the chemoresistant OS cells within the hypoxia core of tumors, thereby preventing survival and metastasis, and ultimately improving the chances of survival amongst OS patients.

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  • 2014-05

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Effects of novel functional food on wellness indicators

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With obesity and metabolic diseases reaching epidemic levels, it is important to find ways to increase physical activity and improve diet. Previous studies have shown that improvements in mood can

With obesity and metabolic diseases reaching epidemic levels, it is important to find ways to increase physical activity and improve diet. Previous studies have shown that improvements in mood can increase desire to perform physical activity, and that vitamin C intake is linked to improvements in mood. Based on this, two hypotheses were formed and tested to investigate the effect on physical activity levels and mood states from vitamin C supplementation at a dose of one gram per day in the form of a novel functional food. Thirty-one college students or faculty at Arizona State University were screened from a pool of applicants and placed into either a vitamin C or placebo group; all participants received the novel functional food to eat daily for four weeks. Serum levels of vitamin C, weight, height, BMI, body fat percentage, mood, and physical activity were measured before and after the functional food intervention. Vitamin C changed significantly through the course of the study in the experimental group. Baseline data for participants showed a positive correlation between vitamin C status and vigor, and a negative correlation between vitamin C status and weight and BMI. Physical activity was not related to vitamin C status, according to baseline data, and it did not significantly change over the course of the study. The results indicate that variance in BMI can be attributed to vitamin C status, but the study should be refined and tested again.

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  • 2014-05

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Evaluation of inflammatory responses and tissue triglyceride concentrations following high fat intake in developing rodents

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High fat diets (HFD) are known to cause hepatic non-alcoholic steatosis in rats in as few as four weeks. Accumulation of triglycerides in liver and skeletal muscle is associated with

High fat diets (HFD) are known to cause hepatic non-alcoholic steatosis in rats in as few as four weeks. Accumulation of triglycerides in liver and skeletal muscle is associated with insulin resistance and obesity. However, studies of fat accumulation in cardiac muscle are not as prevalent. Therefore, the first hypothesis of this study was that HFD would lead to hepatic steatosis as well as lipid accumulation in pectoralis and cardiac muscles, tissues responsible for the majority of postprandial glucose disposal. Prior studies also indicated that HFD leads to increased inflammation and oxidative stress within the vasculature resulting in impaired endothelium-dependent vasodilation, however biomarkers of immune system reactivity were not assessed. Therefore, the second aim of this study was to explore additional pathways of immune system reactivity and stress (natural antibodies; heat shock protein 60 (HSP60)) in rats fed either a control (chow) or high fat (HFD) diet. HSP60 has also recently been recognized as an early marker of vascular dysfunction in humans. The hypothesis was that immune system reactivity and early vascular dysfunction would be heightened in rats fed a HFD compared to chow-fed controls. Young male Sprague-Dawley rats (140-160g) were maintained on a chow diet (5% fat, 57.33% carbohydrate, 3.4kcal/g) or HFD (60% fat, 20% carbohydrate, 5.24 kcal/g) for 6 weeks. HFD rats developed hepatic steatosis with significantly elevated liver triglyceride concentrations compared to chow-fed controls (20.73±2.09 vs.9.75±0.52 mg triglycerides/g tissue, respectively; p=0.001). While lipid accumulation appeared to be evident in the pectoralis muscle from HFD rats, triglyceride concentrations were not significantly different from controls. Likewise, there was no evidence of lipid infiltration in cardiac muscles of HFD rats. Lipid accumulation in the liver of overweight HFD rats may contribute to the observed insulin resistance in these animals. Contrary to the second hypothesis, there were no significant differences in plasma HSP60 expression between HFD and chow rats (p>0.05). Likewise, hemagglutination and hemolysis responses were similar between HFD and chow-fed rats (p>0.05). These findings suggest that immune system responses may not be affected by 6 weeks of high fat intake and that HSP60 is not an early marker of vascular dysfunction in this rodent model.

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  • 2013-05

Comparing Nutritional Physiology and Bioavailable Nutrients between Rural and Urban Populations of Callipepla gambelii

Description

This study is an exploration of the nutritional physiology of Gambel's quail, Callipepla gambelii, in terms of the comparison of rural and urban area populations of this gallinaceous species, and

This study is an exploration of the nutritional physiology of Gambel's quail, Callipepla gambelii, in terms of the comparison of rural and urban area populations of this gallinaceous species, and the employment of in situ study by design. The health of quail populations is of interest as a resource to recreational enthusiasts, hunters, stakeholders, as well as agencies charged with their management. Quail are the only resident small avian game species known to be native to the southwest that is depended upon by management agencies for recreational opportunities. The condition of the Gambel's quail populations determine regulatory actions with respect to recreational quailing opportunities and these quail represent a species which shows adjustment to human expansion. The combination of morphologic, physical, and plasma nutrient data gathered from samples during this study are hypothesized to show a difference between rural and urban populations of C. gambelii. The hypothesis is that urban quail will display morphological differences, and nutrient differences that are crucial to quail fitness, therefore, potential selective differences. Ground and ambient air temperatures are hypothesized to be higher in urban areas andthus these measurements were taken for site comparison. Plasma nutrient concentrations between rural and urban populations of adult male Gambel's quail were compared for potential existing variations in nutrition. The blood nutrient assays are expected to display increased plasma concentrations of constituents such as glucose, lipids, and proteins, which are known to be involved in growth, reproductive success, and general fitness in the urban quail populations. Morphological data was collected to examine the potential differences in the physical attributes of the sampled quail. A fitness advantage in male Gambel's quail living within urban areas is hypothesized to be associated with differences in plasma nutrients and morphology. The potentially differing plasma nutrients in samples of the C. gambelii in urban versus rural environments is believed to be affected by, and to indicate, differing nutrient availability. Body mass and length, chest circumference as well as skin temperatures were measured to assess potential differences in these outward physical attributes. The urban quail are hypothesized to have reproductive and/or natural selective advantages where their measured morphology may show physical size differences. Differences in the physical attributes of the male Gambel's quail that live in urban areas may be supported through measured morphologic attributes.

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  • 2015-12

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Effects of Urbanization and Sex on Color and Disease in the House Finch (Haemorhous mexicanus)

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Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a

Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a surge of interest in how urbanization alters signaling traits, but we know little about if and how cities affect signal expression in female animals. We measured carotenoid-based plumage coloration and coccidian (Isospora spp) parasite burden in desert and city populations of house finches to examine urban impacts on male and female health and attractiveness. In earlier work, we showed that male house finches are less colorful and more parasitized in the city, and we again detected that pattern in this study for males. However, though city females are also less colorful than their rural counterparts, we found that rural females were more parasitized. Also, regardless of sex and unlike rural birds, more colorful birds in the city were more heavily infected with coccidia. These results show that urban environments can disrupt signal honesty in female animals and highlight the need for more studies on how cities affect disease and condition-dependent traits in both male and female animals.

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  • 2016-05

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Diet-Induced Thermogenesis as Measured by Exogenous Norepinephrine Injections in High Fat Diet - Fed Rats: A Pilot Study

Description

It is presently believed that brown adipose tissue (BAT) is an important tissue in the control of obesity because it has the propensity to increase energy expenditure. The purpose of

It is presently believed that brown adipose tissue (BAT) is an important tissue in the control of obesity because it has the propensity to increase energy expenditure. The purpose of this study was to attempt to quantify the thermogenesis of BAT when four rats were exposed to a progression of low-fat to high-fat diet. Exogenous norepinephrine (NE) injections (dose of 0.25 mg/kg i.p.) were administered in order to elicit a temperature response, where increases in temperature indicate increased activity. Temperatures were measured via temperature sensing transponders that had been inserted at the following three sites: interscapular BAT (iBAT), the abdomen (core), and lower back (reference). Data showed increased BAT activity during acute (2-3 weeks) high fat diet (HFD) in comparison to low fat diet (LFD), but a moderate to marked decrease in BAT activity during chronic HFD (6-8 weeks) when compared to acute HFD. This suggests that while a HFD may initially stimulate BAT in the short-term, a long-term HFD diet may have negative effects on BAT activation.

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  • 2016-12

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Is it Hunger or Hormones? Association of Plasma Ghrelin Levels with Eating Behaviors and Weight Cycling History in Obese and Overweight Women

Description

Weight cycling (WC) is characterized by repeated bouts of weight loss followed by regain. WC has been associated with a number of adverse health consequences and is a risk factor

Weight cycling (WC) is characterized by repeated bouts of weight loss followed by regain. WC has been associated with a number of adverse health consequences and is a risk factor for cardiovascular disease. Body weight regulation is complex. Little is known about why women who intentionally lose weight are so likely to regain their weight back. Humans are motivated by a variety of psychological pressures as well as physiological stimuli that influence eating behaviors and weight control. One of the complex factors that has been shown to predict weight regain, in weight-reduced individuals, is hunger. Ghrelin is a known gastrointestinal hormone that rises during weight loss and is a strong trigger of hunger and increased appetite. Increased ghrelin levels have been associated with disordered eating behaviors and active weight loss. The Three Factor Eating Questionnaire (TFEQ-R18) describes elements that may affect hunger and satiety. These factors are: cognitive restraint (CR, defined as regulating food intake because of weight maintenance), uncontrolled eating (UE, defined as difficulty in regulating eating), and emotional eating (EE, refers to the tendency to eat more than needed because of mood state). Objective: The purpose of this study was to explore the associations of fasting plasma ghrelin with eating behaviors and weight cycling in overweight and obese women. Methods: This is a cross-sectional observation of women aged 20-60 years who completed a Weight and Lifestyle Inventory (WALI) and the TFEQ-R18. Women provided a 12-h fasting blood sample and plasma ghrelin was measured using a commercial radioimmunoassay (ELISA kit Cat# EZGRA-88k). Intra- and inter-assay CVs were 88.4% + 13.8% and 84.4% + 8.4% respectively. Descriptive data were computed and Pearson correlations were assessed adjusting for age and body weight (SPSS, v23). Results: A WC Index (WCI) was computed as number of WC reported x the amount of weight lost per cycle. 61 women (mean age: 39.3 + 11 yr; BMI: 31.4 + 7; WCI: 70 + 60; range = 0 to 253) completed questionnaires. Ghrelin was significantly and negatively correlated to weight (R= -0.25, P = 0.03), BMI (R= -0.32, P = .006), UE (R = -0.29, p = 0.02), and EE (R = -0.29, p = 0.04). Ghrelin was not significantly related to WCI. WCI was not significantly correlated with any TFEQ-18 subscales. Conclusion: In this observational study, lower ghrelin was associated with higher UE and EE. Thus physiological hunger sensations from ghrelin secretion, is not a likely stimulus of eating behavior in these women. There are a host of psychological triggers, such as stress, loneliness, guilt, anger etc. that may enhance eating. Future research will need to explore what psychological triggers influence eating behavior and why obese women are resistant to the powerful physiological hunger cues of ghrelin.

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  • 2016-05

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High-Intensity Exercise Preconditioning Prevents Downregulation of eNOS Expression in the Aorta Following Doxorubicin Treatment

Description

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.

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  • 2016-12

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Hepatic inflammatory response following high fat diet in adolescent male Sprague-Dawley rats

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There has long been a link tied between obesity and such pathological conditions as nonalcoholic fatty liver disease and type two diabetes. Studies have shown that feeding rats a diet

There has long been a link tied between obesity and such pathological conditions as nonalcoholic fatty liver disease and type two diabetes. Studies have shown that feeding rats a diet high in fat results in hepatic steatosis and steatohepatitis. Using a novel short term diet of six weeks with male adolescent Sprague-Dawley rats, our laboratory sought to investigate the early effects of high fat intake on the liver. Prior findings in our laboratory found that a high fat diet (HFD) leads to nonalcoholic fatty liver disease as well as other symptoms of metabolic syndrome. This study hypothesized that rats fed a 60% HFD for 6 weeks, unlike a high sucrose or standard chow diet, would have an elevated expression of pro-inflammatory cytokines associated with steatohepatitis. TNF-α, TLR4 and XBP1 were chosen for their link to hepatic inflammation. The results of this study found that contrary to the hypothesis, the high fat diet did not induce significant changes in the expression of any inflammatory marker in comparison to a high sucrose or control chow diet.

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Date Created
  • 2015-05