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We investigate whether applying an internal radiocarpal-spanning plate with the wrist in slight extension affects the biomechanical stability of the construct. An unstable distal radius fracture was simulated in 10 cadaveric specimens and immobilized with a radiocarpal-spanning plate holding the wrist in a neutral position. This construct was then physiologically loaded through the wrist flexor and extensor tendons. The resulting motion at the fracture was captured with a displacement sensor. The plate was then extended using an in situ bending technique, placing the wrist in extension, and the experiment was repeated. No statistically significant difference in the biomechanical stability afforded by the radiocarpal-spanning plate was detected with the wrist in extension compared to that in the traditional neutral position. The radiocarpal-spanning plate fixation was more stable when loaded through the extensor tendons. We conclude that immobilizing a distal radius fracture with an internal radiocarpal-spanning plate that holds the wrist in extension does not compromise biomechanical stability.

Tyrosinase inhibitors are of great clinical interest as agents for the treatment of hyperpigmentary disorders; however, most compounds described in the literature lack clinical efficiency due to insufficient inhibitory activity against human tyrosinase (hTyr). Recently, we reported that thiazolyl resorcinols (4-resorcinylthiazol-2-amines and -amides) are both selective and efficacious inhibitors of hTyr in vitro and in vivo. Here, we measured dose-activity profiles of a large number of thiazolyl resorcinols and analogous compounds to better understand the molecular basis of their interaction with hTyr. We show that both the resorcinyl moiety and the thiazole ring must be intact to allow efficient inhibition of hTyr, while the substituents at the thiazole 2-amino group confer additional inhibitory activity, depending on their size and polarity. The results of molecular docking simulations were in excellent agreement with the experimental data, affording a rationale for the structural importance of either ring. We further propose that a special type of interaction between the thiazole sulfur and a conserved asparagine residue is partially responsible for the superior inhibitory activity of thiazolyl resorcinols against hTyr.