Novel nicotinamide adenine dinucleotide analogues as selective inhibitors of NAD-dependent enzymes

Three novel dinucleotide analogues of nicotinamide adenine dinucleotide (NAD+) have been synthesised from -ribonolactone. These compounds incorporate a thiophene moiety in place of nicotinamide and are hydrolytically stable. They have been evaluated as inhibitors of adenosine diphosphate ribosyl cyclase, glutamate dehydrogenase and Sir2 acyltransferase activities. Enzyme specificity and a high level of inhibition was observed for the dehydrogenase.

On the importance of steady-state isotopic techniques for the investigation of the mechanism of the reverse water-gas-shift reaction

The formation and reactivity of surface intermediates in the reverse water-gas-shift reaction on a Pt/CeO2 catalyst are critically dependent on the reaction conditions so that conclusionsregarding the reaction mechanism cannot be inferred using ex operando conditions.

Characterization and optimization of experimental variables within a reproducible bladder encrustation model and in vitro evaluation of the efficacy of urease inhibitors for the prevention of medical device-related encrustation

This study presents a reproducible, cost-effective in vitro encrustation model and, furthermore, describes the effects of components of the artificial urine and the presence of agents that modify the action of urease on encrustation on commercially available ureteral stents. The encrustation model involved the use of small-volume reactors (700 mL) containing artificial urine and employing an orbital incubator (at 37 degrees C) to ensure controlled stirring. The artificial urine contained sources of calcium and magnesium (both as chlorides), albumin and urease. Alteration of the ratio (% w/w) of calcium salt to magnesium salt affected the mass of encrustation, with the greatest encrustation noted whenever magnesium was excluded from the artificial urine. Increasing the concentration of albumin, designed to mimic the presence of protein in urine, significantly decreased the mass of both calcium and magnesium encrustation until a plateau was observed. Finally, exclusion of urease from the artificial urine significantly reduced encrustation due to the indirect effects of this enzyme on pH. Inclusion of the urease inhibitor, acetohydroxamic acid, or urease substrates (methylurea or ethylurea) into the artificial medium markedly reduced encrustation on ureteral stents. In conclusion, this study has described the design of a reproducible, cost-effective in vitro encrustation model. Encrustation was markedly reduced on biomaterials by the inclusion of agents that modify the action of urease. These agents may, therefore, offer a novel clinical approach to the control of encrustation on urological medical devices. (c) 2005 Wiley Periodicals, Inc.