Xanthine oxidoreductase (XOR) catalyzes the final two reactions that lead to uric acid formation. XOR is a complex molibdoflavoenzyme present in two different functional forms: dehydrogenase and xantine oxidase (XO). XO is a critical source of reactive oxygen species (ROS) that contribute to vascular inflammation. Under normal physiological conditions, it is mainly found in the dehydrogenase form, while in inflammatory situations, posttranslational modification converts the dehydrogenase form into XO. These inflammatory conditions lead to an increase in XO levels and thus an increased ROS generation by the enzymatic process, finally resulting in alterations in vascular function. It has also been shown that XO secondarily leads to peroxynitrite formation. Peroxynitrite is one of the most powerful ROS that is produced by the reaction of nitric oxide and superoxide radicals, and is considered to be a marker for reactive nitrogen species, accompanied by oxidative stress. Febuxostat is a novel nonpurine XO-specific inhibitor for treating hyperuricemia. As febuxostat inhibits both oxidized and reduced forms of the enzyme, it inhibits the ROS formation and the inflammation promoted by oxidative stress. The administration of febuxostat has also reduced nitro-oxidative stress. XO serum levels are significantly increased in various pathological states such as inflammation, ischemia-reperfusion or aging and that XO-derived ROS formation is involved in oxidative damage. Thus, it may be possible that the inhibition of this enzymatic pathway by febuxostat would be beneficial for the vascular inflammation. In animal models, febuxostat treatment has already demonstrated anti-inflammatory effects, together with the reduction in XO activity. However, the role of febuxostat in humans requires further investigation.

3Atta-ur-Rahman and M. Iqbal Choudhary (Eds) All rights reserved-Abstract: Obesity is a multifactorial disease that is currently developing a threatening tendency towards becoming the main cause of chronic disease in the world. Obesity can induce type 2 diabetes mellitus, dyslipidemia, cardiovascular disease and other chronic disorders with high social and health costs. Obesity was firstly described in 2000 as a cardiometabolic disease, even before Metabolic Syndrome, type 2 diabetes mellitus and coronary disease were considered as such. In this chapter we recover this approach to obesity, which has remained almost forgotten for the last decade. In obese subjects, adipokines and miokines interact to promote reticulum stress, insulin resistance, metabolic inflexibility and endothelial dysfunction. These pathological processes are amplified when hyperglycemia is present, leading to an increased risk for atherosclerosis. A number of potential implications for clinical practice are derived from the cardiometabolic state underlying obesity and its comorbidities. The first step in the therapeutic strategy against obesity should be the correct diagnosis of its causes and the promotion of lifestyle changes including physical exercise and a healthy diet. In the usual case of failing to achieve results, we can still resort to the pharmacological therapy. While awaiting the release of new drugs, topiramate, alone or combined with phentermine, has been proposed as a novel anti-obesity drug, showing relevant effects not only on weight loss but also on cardiometabolic alterations and biomarkers, even though new studies should clarify the mechanisms of these findings. Finally, our own experience with topiramate is described, focusing on its effects upon weight loss and inflammatory markers.