Several experimental and clinical studies have shown that oxidized low-density lipoprotein and oxidation-sensitive mechanisms are central in the pathogenesis of vascular dysfunction and atherogenesis. Here, we have used p66 Shc؊/؊ and WT mice to investigate the effects of high-fat diet on both systemic and tissue oxidative stress and the development of early vascular lesions. To date, the p66 Shc؊/؊ mouse is the unique genetic model of increased resistance to oxidative stress and prolonged life span in mammals. Computer-assisted image analysis revealed that chronic 21% highfat treatment increased the aortic cumulative early lesion area by Ϸ21% in WT mice and only by 3% in p66 Shc؊/؊ mice. Early lesions from p66 Shc؊/؊ mice had less content of macrophage-derived foam cells and apoptotic vascular cells, in comparison to the WT. Furthermore, in p66 Shc؊/؊ mice, but not WT mice, we found a significant reduction of systemic and tissue oxidative stress (assessed by isoprostanes, plasma low-density lipoprotein oxidizability, and the formation of arterial oxidation-specific epitopes). These results support the concept that p66 Shc؊/؊ may play a pivotal role in controlling systemic oxidative stress and vascular diseases. Therefore, p66 Shc might represent a molecular target for therapies against vascular diseases.atherosclerosis ͉ oxygen radicals ͉ transgenic mouse T he p66Shc protein is one of the three isoforms encoded by the mammalian Shc locus. The Shc overlapping proteins (p66 Shc , p52 Shc , and p46 Shc ) share a C-terminal Src homology 2 (SH2) domain, a central collagen-homologous (CH) region, and an N-terminal phosphotyrosine binding domain and differ for N termini of different lengths. P66 Shc , in particular, is characterized by an additional CH region at the N terminus. Shc proteins are cytoplasmic substrates of activated tyrosine kinases and have been implicated in the transmission of activation signals from tyrosine kinases to Ras proteins (1-3). In 1999, it became clear that Shc proteins might serve broad cellular functions. Homozygous mutation of p66Shc in mice was shown to induce increased resistance to oxidative stress and lifespan extension (4). Recently, it has been demonstrated that the p66 Shc longevity gene increases intracellular reactive oxygen species (ROS), thereby affecting the rate of oxidative damage to nucleic acids; in advance p66 Shc function on ROS, metabolism is necessary for appropriate p53-dependent apoptosis (5).Cells within the arterial wall produce several species of free radicals, and, as is well known, an important functional index of healthy status is represented by vascular function (reviewed in refs. 6 and 7). A multitude of clinical studies and reports with experimental animal models have shown that oxidized lowdensity lipoprotein (oxLDL) and redox-sensitive pathways are key modulators of vascular dysfunction and atherogenesis (reviewed in refs. 8-10). Interestingly, oxLDL and its byproducts may induce early proatherogenic events not only in adults but also in arteries of the ...

Body packing represents the concealment of illegal substances in a person's body with the aim of smuggling. "Body packers" either swallow drug-filled packets or introduce drug-filled packets into their bodies rectally or vaginally with the purpose of concealing them. The three main smuggled drugs are cocaine, heroin and cannabis products. Body packing represents a serious risk of acute narcotic toxicity from drug exposure, intestinal obstruction owing to pellet impaction and bowel perforation with consequent abdominal sepsis. A suspected body packer is generally admitted to hospital to perform imaging investigations and confirm the presence of drugs in his/her body. Radiological imaging methods are essential to diagnose body packing and to detect potential complications. Increasing sophistication of traffickers and improvements in packaging add to the detection difficulty. Radiologists should be aware of the appearance of drug packets in a range of imaging modalities. This article informs physicians about the challenging aspects of body packing, its background and medicolegal issues, what imaging methods can be used and what criteria are necessary to perform a correct diagnosis.

CorrectionsPHARMACOLOGY. For the article ''Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress,'' by Filomena de Nigris, Lilach O. Lerman, Sharon Williams Ignarro, Giacomo Sica, Amir Lerman, Wulf Palinski, Louis J. Ignarro, and Claudio Napoli, which appeared in issue 3, February 4, 2003, of Proc. Natl. Acad. Sci. USA (100, 1420-1425