University of Kentucky

About: University of Kentucky is a education organization based out in Lexington, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 43933 authors who have published 92195 publications receiving 3256087 citations. The organization is also known as: UK.

Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2.

Abstract: Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. Resveratrol was also shown to confer vasoprotection in animal models of type 2 diabetes and aging. However, the mechanisms by which resveratrol exerts its antioxidative vasculoprotective effects are not completely understood. Using a nuclear factor-E2-related factor-2 (Nrf2)/antioxidant response element-driven luciferase reporter gene assay, we found that in cultured coronary arterial endothelial cells, resveratrol, in a dose-dependent manner, significantly increases transcriptional activity of Nrf2. Accordingly, resveratrol significantly upregulates the expression of the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1, γ-glutamylcysteine synthetase, and heme oxygenase-1. Resveratrol treatment also significantly attenuated high glucose (30 mM)-induced mitochondrial and cellular oxidative stress (assessed by flow cytometry using MitoSox and dihydroethidine staining). The aforementioned effects of resveratrol were significantly attenuated by the small interfering RNA downregulation of Nrf2 or the overexpression of Kelch-like erythroid cell-derived protein 1, which inactivates Nrf2. To test the effects of resveratrol in vivo, we used mice fed a high-fat diet (HFD), which exhibit increased vascular oxidative stress associated with an impaired endothelial function. In HFD-fed Nrf2+/+ mice, resveratrol treatment attenuates oxidative stress (assessed by the Amplex red assay), improves acetylcholine-induced vasodilation, and inhibits apoptosis (assessed by measuring caspase-3 activity and DNA fragmentation) in branches of the femoral artery. In contrast, the aforementioned endothelial protective effects of resveratrol were diminished in HFD-fed Nrf2−/− mice. Taken together, our results indicate that resveratrol both in vitro and in vivo confers endothelial protective effects which are mediated by the activation of Nrf2.

Increased Nuclear DNA Oxidation in the Brain in Alzheimer's Disease

Abstract: Multiple lines of evidence indicate that oxidative stress is a contributor to neuronal death in Alzheimer's disease (AD). The oxidative damage that occurs to DNA may play a role in both normal aging and neurodegenerative diseases, including AD. This is a study of the oxidative damage that occurs in nuclear DNA in the brains of AD patients and cognitively intact, prospectively evaluated, age-matched control subjects. Nuclear DNA from frontal, temporal, and parietal lobes and cerebellum was isolated from 11 control subjects and 9 AD subjects, and oxidized purine and pyrimidine bases were quantitated using gas chromatography/mass spectrometry. Stable isotope-labeled oxidized base analogues were used as internal standards to measure 5-hydroxyuracil, 5-hydroxycytosine, 8-hydroxyadenine, 4,6-diamino-5-formamidopyrimidine (Fapy-adenine), 8-hydroxyguanine, and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy-guanine). Statistically significant elevations of 5-hydroxycytosine, 5-hydroxyuracil, 8-hydroxyadenine, and 8-hydroxyguanine were found in AD brain compared with control subjects (p < 0.05). There was an increased trend in the levels of Fapy-adenine in the AD brain, and Fapy-guanine showed a trend toward higher levels in control brains compared with AD. A generally higher level of oxidative DNA damage was present in neocortical regions than cerebellum. No significant correlation was observed between the oxidized bases and neurofibrillary tangle and senile plaque counts. Our results demonstrate that nuclear DNA damage by oxygen-derived radicals is increased in AD and support the concept that the brain is under increased oxidative stress in AD.

Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer

Abstract: A set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with thyroid nodules or thyroid cancer was developed by consensus by an 11-member Standards of Care Committee (the authors of the article) of the American Thyroid Association, New York, NY. The participants were selected by the committee chairman and by the president of the American Thyroid Association based on their clinical experience. The committee members represented different geographic areas within the United States, to reflect different practice patterns. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. Each committee participant was initially assigned to write a section of the document and to submit it to the committee chairman, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. Several of the committee members further revised and refined the document, which was then submitted to the entire membership of the American Thyroid Association for written comments and suggestions, many of which were incorporated into a final draft document, which was reviewed and approved by the Executive Council of the American Thyroid Association.

Putting Parties in Their Place: Inferring Party Left-Right Ideological Positions from Party Manifestos Data

Abstract: The left-right ideological positions of political parties play a central role in theorizing about many different aspects of democratic processes. Unfortunately, scholars are hindered in their ability to test existing theories by the limited availability of data that is comparable over time and across countries. This paper describes a simple 'vanilla' method for using manifestos data to estimate party leftright positions. It then tests this method and four existing ones by regressing a variety of accepted survey-based measures of left-right party positions on the estimates of party positions generated by the various techniques. Finally, analysis of the residuals from these regressions identifies the extent to which there are systematic sources of errors in using manifestos data to estimate party left-right positions. The vanilla method consistently produces the best estimates of party positions, and these estimates are quite good (less than one point, on average, from the estimates of other accepted approaches). Manifestos data, however, tend to locate extreme parties closer to the ideological center than do other survey-based approaches. he left-right ideological positions of political parties play a central role in theorizing many different aspects of democratic processes. Scholars employ the left-right positions of parties in theoretical arguments and empirical tests on such topics as macro-economic policymaking, legislative institutional choice, electoral competition, voting behavior, political representation, and cabinet stability. Thus, evaluation of a wide range of theoretical arguments in comparative politics requires reliable measures of the left-right positions of political parties. A practical problem facing scholars, however, is the limited availability of appropriate measures. There are two common sources of data on leftright party locations. One consists of expert surveys on specific party systems, where experts are asked to provide estimates of party left-right positions in these systems. Castles and Mair (1984) published the first such survey in a large number of countries, and results from a similar, subsequent survey are presented in Huber and Inglehart (1995).' Although these surveys are widely used to measure party positions, they suffer important limitations: they have been administered infrequently, in different formats, and only over the last fifteen years. A second source of data is the left-right positions of party supporters as reported in mass surveys such as the Eurobarometer or the World Values Survey. These surveys have been administered more frequently, but only over the last two decades and for a limited number of countries. Thus, scholars are frequently forced to limit their