Mounir J. Haurani

Differential effect of zoledronic acid on human vascular smooth muscle cells

INTRODUCTIONnThe 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.nnnMETHODSnHuman aortic smooth muscle cells (HASMC) were cultured under either proliferating or growth arrest (quiescent) conditions in the presence or absence of ZA for 48xa0hours, 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.nnnRESULTSnThere 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.nnnCONCLUSIONSnThese 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.

Physician satisfaction with the vascular lab is highly dependent on after hour's availability

Physicians and mid-level providers often order Vascular Laboratory (VL) testing because the studies performed are noninvasive, relatively in expensive, can help direct clinical decision making and can easily be performed both in the lab and in a portable fashion. This offers a versatility that other imaging modalities cannot always provide. Hospitals rely on accreditation agencies (Intersocietal Accreditation Commission, IAC) to set standards which emphasize technical proficiency and quality measures. However, to gauge general satisfaction with the facility, services and medical care they either perform patient satisfaction surveys in various departments themselves or hire consultants. Although hospitals also assess physician satisfaction with various functions within the hospital, physician satisfaction with specifically VL services has not been previously reported.