Differential effect of zoledronic acid on human vascular smooth muscle cells.

INTRODUCTION: The activation of human vascular smooth muscle cell proliferation, adhesion and migration is essential for intimal hyperplasia formation. These experiments were designed to test whether zoledronic acid (ZA) would modulate indices of human smooth muscle cell activation, exert differential effects on proliferating versus quiescent cells, and determine whether these effects were dependent on GTPase binding proteins prenylation. ZA was chosen for testing in these experiments because it is clinically used in humans with cancer, and has been shown to modulate rat smooth muscle cell proliferation and migration. METHODS: Human aortic smooth muscle cells (HASMC) were cultured under either proliferating or growth arrest (quiescent) conditions in the presence or absence of ZA for 48 hours, whereupon the effect of ZA on HASMC proliferation, cellular viability, metabolic activity, and membrane integrity were compared. In addition, the effect of ZA on adhesion and migration were assessed in proliferating cells. The effect of increased concentration of ZA on the mevalonate pathway and genomic/cellular stress related poly-adenosine diphosphate ribose polymerase enzyme activity were assessed using the relative prenylation of Rap-1A/B protein and the formation of poly adenosine diphosphate-ribosylated protein, respectively. RESULTS: There was a dose dependent inhibition of cellular proliferation, adhesion and migration following ZA treatment. ZA treatment decreased indices of cellular viability and significantly increased membrane injury in proliferating versus quiescent cells. This was correlated with the appearance of unprenylated Rap-1A protein and dose dependent down regulation of activity. CONCLUSIONS: These data suggest that ZA is effective in inhibiting HASMC proliferation, adhesion, and migration, which coincide with the appearance of unprenylated RAP-1A/B protein, thereby suggesting that the mevalonate pathway may play a role in the inhibition of HASMC activation.

Demystifying Small Concha-type Microtia: Advancements in Classification and Surgical Approach.

The accurate identification of microtia type is foundational to preoperative planning and intraoperative strategies for auricular reconstruction using an autologous costal cartilage framework. Although the repair of lobule type microtia has similarities to that of small concha-type, the latter has specific nuances that must be considered to optimize functional and aesthetic outcomes. The article describes the senior author's advancements in repair of all microtia types: use of an "auricular rectangle" to determine ideal ear placement, W-flap manipulation for vestige transposition, and skin trimming. The additional focus on small concha-type microtia addresses common errors in identification and reconstruction of the conchal bowl.