Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects

Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects.J.L. Hay, S.F. La Vincente, A.A. Somogyi, C.B. Chapleo, J.M. Whit

Grain Boundary Serration in Nickel-Based Superalloy Inconel 600: Generation and Effects on Mechanical Behavior

Grain boundary serration in the superalloy Inconel 600 was studied. Two microstructural variants, one with nonserrated and the other with serrated grain boundaries were generated by altering the heat-treatment conditions, while keeping other aspects of the microstructure unchanged. The effect on the creep response between 700 °C and 900 °C was measured, and the different failure modes and accumulated damage were quantified using high-angular resolution electron backscatter diffraction analysis in the scanning electron microscope and also by X-ray computed tomography. It is found that serration plays a more crucial role in the high-temperature/low-stress regime when an intergranular cracking mechanism involving cavitation is operative; here it plays a role in improving both creep life and creep ductility. Any effect of serration is less prevalent at low temperatures where transgranular failure is dominant