Xanthine oxidoreductase (XOR), a complex flavoprotein, catalyzes the metabolic reactions leading from hypoxanthine to xanthine and from xanthine to urate, and both reactions take place at the molybdenum cofactor. The enzyme is a target of drugs for therapy of gout or hyperuricemia. We review the chemical nature and reaction mechanisms of the molybdenum cofactor of XOR, focusing on molybdenum-de...

37 37 GENERIC NAME PAGE Allopurinol 445 Colchicine 443 Indomethacin 446 Oxyphenbutazone 446 GENERIC NAME PAGE Oxypurinol 446 Phenylbutazone 446 Probenecid 445 Sulfinpyrazone 445 Gout is characterized biochemically as a disorder of uric acid metabolism and clinically by hyperuricemia and recurrent attacks of acute arthritis. Gouty arthritis is most frequently seen as an acute inflammation primar...

In studies conducted in vitro, it has been demonstrated that estrogen has an antioxidant potential that may contribute to its protective effects on the cardiovascular system. However, the antioxidant effect of estrogen in vivo has not been demonstrated. To address this issue, in this study the effects of estrogen on oxidative stress were evaluated in microvessels studied in vivo. Oxidative stre...

BACKGROUND Xanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated...

URIC ACID METABOLISM AND ATRIAL REMODELING Potential sources and factors implicated in AF-related oxidative stress include NADPH oxidase activation, calcium overloading and mitochondrial damage, angiotensin system activation, NO synthase uncoupling, XO activation, altered expression of redoxrelated genes, other genetic factors, aging, obesity, and other associated cardiovascular conditions (Kor...

The enzyme is well-suited to carry out the catalysis of these oxidative reactions, containing as it does four redox-active sites: molybdenum, flavin adenine dinucleotide (FAD) and a pair of iron-sulfur centers of the ferredoxin type (Fe2S2). The purine substrates interact with the enzyme at the molybdenum site of xanthine oxidase and oxygen at the flavin site. The two metabolic reactions above ...

The relevance of elevated plasma levels of serum uric acid (SUA) in patients with cardiovascular disease was historically described 2 centuries century ago when Alexander Heig published a paper dealing with the causative role of hyperuricermia in patients with hypertension and several other diseases. More recently, a remarkable number of epidemiological and experimental studies have demonstrate...

Some of the most therapeutically interesting natural products are mixed polyketide/nonribosomal peptide molecules, including bleomycin and epothilones (anticancer agents) and FK506 and rapamycin (immunosuppressive drugs).1-3 These enzymatically assembled molecules are encoded by multimodular protein arrays that, through their chain-ordering, determine the structure of the natural product elonga...

In this paper, we rst summarize the research that has been completed in the eld of DNA computing and the research problems that must be overcome if the technique of computing with molecules is to become practical. We then propose a new direction in research towards autonomous molecular computers , describe the author's work on the implementation of state machines using DNA molecules, and discus...

Out of hours investigations are no longer used exclusively for diagnosis leading to urgent treatment. Deleting tests that do not meet traditional criteria of urgency might thus lead to additional costs for example, by delaying discharge of a patient at the weekend or necessitating earlier admission so that preoperative tests could be done during normal working hours. Although the need to reduce...