Potential Assessment of UGT2B17 Inhibition by Salicylic Acid in Human Supersomes In Vitro

Glucuronidation is a Phase 2 metabolic pathway responsible for the metabolism and excretion of testosterone to a conjugate testosterone glucuronide. Bioavailability and the rate of anabolic steroid testosterone metabolism can be affected upon UGT glucuronidation enzyme alteration. However, there is a lack of information about the in vitro potential assessment of UGT2B17 inhibition by salicylic acid. The purpose of this study is to investigate if UGT2B17 enzyme activity is inhibited by salicylic acid. A UGT2B17 assay was developed and validated by HPLC using a C18 reversed phase column (SUPELCO 25 cm × 4.6 mm, 5 μm) at 246 nm using a gradient elution mobile phase system: (A) phosphate buffer (0.01 M) at pH = 3.8, (B) HPLC grade acetonitrile and (C) HPLC grade methanol. The UGT2B17 metabolite (testosterone glucuronide) was quantified using human UGT2B17 supersomes by a validated HPLC method. The type of inhibition was determined by Lineweaver–Burk plots. These were constructed from the in vitro inhibition of salicylic acid at different concentration levels. The UGT2B17 assay showed good linearity (R2 > 0.99), acceptable recovery and accuracy (80–120%), good reproducibility and acceptable inter and intra-assay precision (<15%), low detection (6.42 and 2.76 μM) and quantitation limit values (19.46 and 8.38 μM) for testosterone and testosterone glucuronide respectively, according to ICH guidelines. Testosterone and testosterone glucuronide were found to be stable up to 72 h in normal laboratory conditions. Our investigational study showed that salicylic acid uncompetitively inhibited UGT2B17 enzyme activity. Thus, drugs that are substrates for the UGT2B17 enzyme have negligible potential effect of causing interaction with salicylic acid in humans.     

The similarity solution for a bore on a beach

A similarity solution is found for the asymptotic behavior of a bore as it approaches the shoreline on a sloping beach. This gives direct confirmation of earlier results on the motion of the bore and adds details of the associated flow field. It also makes explicit the analogy with Guderley's implosion problem in gas dynamics; the solution is constructed closely following Guderley's arguments.     

Tornehave morphisms, II: The lifted Tornehave morphism and the dual of the Burnside functor

We introduce the lifted Tornehave morphism , an inflation Mackey morphism for finite groups, π being a set of primes, K the kernel of linearization, and B^∗ the dual of the Burnside functor. For p-groups, is unique up to scalar multiples. It induces two morphisms of biset functors, one with a codomain associated with a subgroup of the Dade group, the other with a codomain associated with a quotient of the Burnside unit group.     

Laser interferometry in shock-wave research

The various laser-interferometer instrumentation techniques which have been applied to the study of plane-stress-wave propagation in solids are reviewed and discussed. The capabilities and limitations of present systems are described.