Simvastatin suppresses experimental aortic aneurysm expansion

ObjectiveAbdominal aortic aneurysm (AAA) formation is a result of inflammation and extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases (MMPs). Hydroxymethylglutaryl-coenzyme A inhibitors (statins), although clinically used as lipid-lowering agents, have also been demonstrated to have anti-inflammatory effects. This study was designed to determine whether the hydroxymethylglutaryl-coenzyme A inhibitor simvastatin suppresses aneurysm formation in an elastase-induced rat AAA model.MethodsAneurysms were created in adult male Wistar rats by infusion of elastase into isolated infrarenal aortic segments. The rats were randomized to receive either simvastatin (n = 17) or placebo (n = 17) by gastric lavage daily starting the day before surgery. The rats were euthanized and the infrarenal aortas harvested on postoperative day 7. Aortic diameters were measured before infusion, immediately after infusion, and at the time of harvesting. Protein expression was measured by immunoblot analysis. Gene expression profiling using Affymetrix U34A rat genome chips was performed to identify changes in gene expression caused by simvastatin treatment.ResultsMean aneurysm diameter was significantly less in the simvastatin treatment group compared with controls (3.4 ± 0.08 mm vs 4.3 ± 0.19 mm; P = .0001). MMP-9 and nuclear factor-κB protein levels were decreased in the aortas of simvastatin-treated animals. Gene microarray analysis revealed 315 genes with statistically significant changes in expression (P < .05) in the simvastatin group. Genes related to inflammation, ECM remodeling, and oxidative stress function were downregulated. These included genes for interleukin 1, interleukin 4, inducible nitric oxide synthase, P-selectin, platelet-derived growth factor α, tumor necrosis factor, and several chemokines.ConclusionsSimvastatin significantly suppresses experimental aneurysm expansion and reduces protein levels of MMP-9 and nuclear factor-κB. Gene array analysis provides evidence that several mediators of inflammation, matrix remodeling, and oxidative stress are downregulated by simvastatin treatment. This suggests that simvastatin inhibits AAA formation by blocking the expression of certain proinflammatory genes. Simvastatin may be useful as an adjuvant therapy to suppress the growth of small aneurysms.Clinical RelevanceHuman aortic aneurysms are characterized histologically by an inflammatory infiltrate with severe proteolytic destruction. Statins, although used clinically as lipid-lowering agents, have been shown to have anti-inflammatory effects. Simvastatin reduced experimental aneurysm size in this study. It seems that this reduction is mediated by interfering with multiple pathways, including oxidative stress, inflammation, and ECM and matrix remodeling. Further study into the effect of statins in reducing the growth of AAAs in patients is warranted

Toward a Comprehensive Approach to the Collection and Analysis of Pica Substances, with Emphasis on Geophagic Materials

Pica, the craving and subsequent consumption of non-food substances such as earth, charcoal, and raw starch, has been an enigma for more than 2000 years. Currently, there are little available data for testing major hypotheses about pica because of methodological limitations and lack of attention to the problem.In this paper we critically review procedures and guidelines for interviews and sample collection that are appropriate for a wide variety of pica substances. In addition, we outline methodologies for the physical, mineralogical, and chemical characterization of these substances, with particular focus on geophagic soils and clays. Many of these methods are standard procedures in anthropological, soil, or nutritional sciences, but have rarely or never been applied to the study of pica.Physical properties of geophagic materials including color, particle size distribution, consistency and dispersion/flocculation (coagulation) should be assessed by appropriate methods. Quantitative mineralogical analyses by X-ray diffraction should be made on bulk material as well as on separated clay fractions, and the various clay minerals should be characterized by a variety of supplementary tests. Concentrations of minerals should be determined using X-ray fluorescence for non-food substances and inductively coupled plasma-atomic emission spectroscopy for food-like substances. pH, salt content, cation exchange capacity, organic carbon content and labile forms of iron oxide should also be determined. Finally, analyses relating to biological interactions are recommended, including determination of the bioavailability of nutrients and other bioactive components from pica substances, as well as their detoxification capacities and parasitological profiles.This is the first review of appropriate methodologies for the study of human pica. The comprehensive and multi-disciplinary approach to the collection and analysis of pica substances detailed here is a necessary preliminary step to understanding the nutritional enigma of non-food consumption

Common femoral artery injury secondary to bicycle handlebar trauma

AbstractBlunt trauma from bicycle handlebars is associated with well-described injuries of the abdominal viscera. These injuries result from the forceful compression of the relatively immobile abdominal organs between the handlebar end and the vertebral bodies. The common femoral artery is also immobile as it passes anterior to the superior pubic ramus, rendering this vessel susceptible to a similar mechanism of injury. We have treated two children who sustained thrombosis of the common femoral artery caused by bicycle handlebar trauma. The lack of familiarity with this uncommon mode of injury may contribute to delayed diagnosis and increased morbidity. We therefore wish to draw attention to this mechanism of injury. (J Vasc Surg 2002;35:589-91.