Curcumin inhibits Homocysteine-induced endothelial dysfunction in porcine coronary arteries

Curcumin inhibits Homocysteine-induced endothelial dysfunction in porcine coronary arteries

291 ASSOCIATION FOR ACADEMIC SURGERY—ABSTRACTS both relative to shams (P ⬍ 0.05), but no difference in activity was found. MMP-14 expression was 2- t...

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ASSOCIATION FOR ACADEMIC SURGERY—ABSTRACTS both relative to shams (P ⬍ 0.05), but no difference in activity was found. MMP-14 expression was 2- to 3.6-fold greater at day 12 compared to earlier time points and shams (P ⬍ 0.001), but no difference in protein levels was found. Plasminogen activator inhibitor was increased at 4 days relative to sham, but not after 8 days. Procollagen I and III increased over time and peaked at 12 days (24-fold, 6.1-fold, respectively, P ⬍ 0.02). Conclusions. Vein wall remodeling after DVT is associated with persistent procollagen up regulation and primarily MMP-2 expression and activity, whereas other proteases may be less important. 58. First Measurement of Mechanical Cell Loading. A. Voorhees, MS, T. Wei, PHD, and G.B. Nackman, MD. Robert Wood Johnson Medical School. Endothelial cells experience shear and pressure forces (dependent on flow and cell shape), which have been estimated computationally. Varying importance of the role and magnitude of pressure has been noted. For the first time, actual total mechanical loading was measured experimentally on cells with a novel bioreactor. Human Endothelial Cells (ECs) cultured on Dacron were exposed to 4 dyn/cm2 of continuous wall shear stress (SS) in a flow device allowing visualization of cells by fluorescent microscopy and performance of ␮scale particle image velocimetry. Particles were seeded into medium, laser illuminated, and imaged to determine velocity. Measurements made in multiple planes created 3-dimensional information. SS at a location on fluorescently labeled ECs was quantified using the difference between adjacent velocity vectors divided by the physical spacing between the vectors, providing the cell membrane location (surface height) and SS. The pressure field over cells was calculated by solving the Navier–Stokes equations and integrated over the measurement plane. SS on the cell

varied between 3.7 and 5.0, mean 4.3 dyn/cm2. The peak values of SS were noted in regions of higher elevation. The pressure varied ⫾ 1.5 dyn/cm 2 above mean. High- and low-pressure zones were observed, upstream and downstream, of an elevated region. The pressure over a cell is on the order of the SS, thus finally proving the necessity for considering both pressure and shear stress effects on endothelial cells. Cell adaptation to force can now be studied, allowing coupled, dynamically changing, measurements of load and response. 59. Curcumin Inhibits Homocysteine-Induced Endothelial Dysfunction in Porcine Coronary Arteries. G. Ramaswami, MD, PhD, H. Chai, MD, PhD, Q. Yao, MD, PhD, P. Lin, MD, A.B. Lumsden, MD, and C. Chen, MD, PhD. Baylor College of Medicine. Background. Curcumin, a yellow polyphenolic compound from the plant Curcuma ionga, has anti-tumor, anti-inflammatory, and antioxidant activities. The aim of this study was to determine the effect of

curcumin on homocysteine (HCY)-induced endothelial dysfunction and superoxide anion production in a porcine coronary artery model. Methods. Five-millimeter porcine coronary artery rings from 8 hearts were incubated for 24 h as either controls, with HCY (50 ␮M), curcumin (5 ␮M), or a combination of curcumin (5 ␮M) and HCY (50 ␮M). Following this, vasomotor function was analyzed with a myograph device in response to thromboxane A2 analogue U466419, bradykinin, and sodium nitroprusside (SNP), respectively. Additionally, superoxide anion production was determined by lucigenin-enhanced chemiluminescence assay. Results. All groups of porcine coronary artery rings showed no difference in maximal contraction in response to U46619. However, endothelium-dependent relaxation (bradykin) was 40% in the HCYtreated group as compared to 73% in controls (P ⫽ 0.03, n ⫽ 8). The curcumin plus HCY group showed a significant improvement of endothelium-dependent relaxation as compared to the HCY-treated group (P ⫽ 0.04), but no difference over controls. Curcumin alone showed no difference with controls. All groups showed no difference in endothelium-independent relaxation. Superoxide levels was 13.3 ⫾ 2.1 RLU/s/mm 2 in control vessels, 40.5 ⫾ 8.7 RLU/s/mm2 in HCY-treated vessels, 20.0 ⫾ 2.2 RLU/s/mm2 in curcumin treated vessels, and 10.0 ⫾ 1.9 RLU/s/mm2 in HCY plus curcumin-treated vessels. Conclusion. These results show that curcumin effectively reverses the endothelial dysfunction induced by HCY. Additionally, curcumin also significantly decreases HCY-induced superoxide production. This study may suggest a therapeutic role of dietary curcumin for patients with hyperhomocysteinemia, thereby reducing cardiovascular morbidity and mortality.

EDUCATION PARALLEL SESSION 60. How Should Medical Student Surgical Rotations be Structured to Optimize Education? S.M. Weber, MD, J. Fergestad, MD, B. Lewis, G. Tefera, MD, and H. Chen, MD. University of Wisconsin. Introduction. Surgical rotations for medical students have traditionally been service-based, with students observing surgical cases specific to an area of concentration specific to their assigned service. This may result in a lack of exposure to all surgical fields. To overcome this problem, students can rotate through focused “mini-rotations” in surgical subspecialties. We evaluated improvements in knowledge for students exposed to two types of surgical education: (1) traditional servicebased rotations and (2) focused mini-rotations through surgical subspecialties. Methods. Third-year medical students (n ⫽ 281) were assigned to a 4-week rotation on one of three services, with one service having a focused exposure to endocrine surgery: (1) surgical oncology/ endocrine, (2) trauma, (3) general surgery. Students on all rotations were required to do a “mini-rotation” on vascular surgery for 2 days. To determine if there was a difference in learning between service-based (endocrine) versus “mini-rotation-based” (vascular) approaches to surgical education, a pre- and postrotation endocrine/vascular exam was administered. Results. All students performed similarly on the prerotation test. However, students who had exposure to endocrine surgery had larger improvements on test scores. Reflecting the fact that all students had exposure to vascular surgery during this time, there was no difference in vascular exam scores. Conclusion. Service-based ro-

TABLE—ABSTRACT 60 % Improvement on test Service

n

Endocrine

Vascular

Surg onc/endocrine Trauma General surgery Total

84 80 117 281

*21.1 9.5 14.6 *P ⬍ 0.05

16.0 17.9 12.0 P ⫽ NS