Objectives-Obesity causes inflammation and insulin resistance in the vasculature as well as in tissues involved in glucose metabolism such as liver, muscle, and adipose tissue. To investigate the relative susceptibility of vascular tissue to these effects, we determined the time course over which inflammation and insulin resistance develops in various tissues of mice with diet-induced obesity (DIO) and compared these tissue-based responses to changes in circulating inflammatory markers. Methods and Results-Adult male C57BL/6 mice were fed either a control low-fat diet (LF; 10% saturated fat) or a high-fat diet (HF, 60% saturated fat) for durations ranging between 1 to 14 weeks. Cellular inflammation and insulin resistance were assessed by measuring phospho-IB␣ and insulin-induced phosphorylation of Akt, respectively, in extracts of thoracic aorta, liver, skeletal muscle, and visceral fat. As expected, HF feeding induced rapid increases of body weight, fat mass, and fasting insulin levels compared to controls, each of which achieved statistical significance within 4 weeks. Whereas plasma markers of inflammation became elevated relatively late in the course of DIO (eg, serum amyloid A [SAA], by Week 14), levels of phospho-IB␣ in aortic lysates were elevated by 2-fold within the first week. The early onset of vascular inflammation was accompanied by biochemical evidence of both endothelial dysfunction (reduced nitric oxide production; induction of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1) and insulin resistance (impaired insulin-induced phosphorylation of Akt and eNOS). Although inflammation and insulin resistance were also detected in skeletal muscle and liver of HF-fed animals, these responses were observed much later (between 4 and 8 weeks of HF feeding), and they were not detected in visceral adipose tissue until 14 weeks. Conclusions-During obesity induced by HF feeding, inflammation and insulin resistance develop in the vasculature well before these responses are detected in muscle, liver, or adipose tissue. This observation suggests that the vasculature is more susceptible than other tissues to the deleterious effects of nutrient overload.

High intensity focused ultrasound (HIFU), is a promising, non-invasive modality for treatment of tumours in conjunction with magnetic resonance imaging or diagnostic ultrasound guidance. HIFU is being used increasingly for treatment of prostate cancer and uterine fibroids. Over the last 10 years a growing number of clinical trials have examined HIFU treatment of both benign and malignant tumours of the liver, breast, pancreas, bone, connective tissue, thyroid, parathyroid, kidney and brain. For some of these emerging indications, HIFU is poised to become a serious alternative or adjunct to current standard treatments--including surgery, radiation, gene therapy, immunotherapy, and chemotherapy. Current commercially available HIFU devices are marketed for their thermal ablation applications. In the future, lower energy treatments may play a significant role in mediating targeted drug and gene delivery for cancer treatment. In this article we introduce currently available HIFU systems, provide an overview of clinical trials in emerging oncological targets, and briefly discuss selected pre-clinical research that is relevant to future oncological HIFU applications.

OBJECTIVE. A recent publication has drawn attention to the anterolateral ligament, a structure of the knee with which most radiologists are unfamiliar. We evaluate this structure on MRI; clarify its origin, insertion, meniscal relationship, and morphologic appearance; and identify its relationship with the Segond fracture. MATERIALS AND METHODS. A total of 53 routine knee MRI studies interpreted as normal were reviewed to characterize the anterolateral ligament. A further 20 knee MRI studies with a Segond fracture were assessed to determine a relationship between the fracture and the anterolateral ligament. RESULTS. In all 53 cases, a structure was present along the lateral knee connecting the distal femur to the proximal tibia, with meniscofemoral and meniscotibial components. This structure was somewhat ill defined and sheetlike, inseparable from the adjacent fibular collateral ligament proximally and iliotibial band distally. Aside from one case limited by anatomic distortion, all cases with a Segond fracture exhibited attachment of this structure to the fracture fragment (19/20 cases). CONCLUSION. An ill-defined sheetlike structure along the lateral knee exists attaching the distal femur, body of lateral meniscus, and proximal tibia. This structure has been referenced in the literature dating back to Paul Segond's original description of the Segond fracture in 1879. The structure is identifiable on MRI and appears to be attached to the Segond fracture fragment. For the radiologist, it may be best to forgo an attempt to separate this structure into discrete divisions, such as the anterolateral ligament, because these individual components are inseparable on routine MRI.

Objective-We investigated whether NADPH oxidase-dependent production of superoxide contributes to activation of NF-B in endothelial cells by the saturated free fatty acid palmitate. Methods and Results-After incubation of human endothelial cells with palmitate at a concentration known to induce cellular inflammation (100 mol/L), we measured superoxide levels by using electron spin resonance spectroscopy and the spin trap 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). Palmitate exposure induced a Ͼ2-fold increase in superoxide levels, an effect associated with activation of NF-B signaling as measured by phospho-IB␣, NF-B activity, IL-6, and ICAM expression. Reduction in superoxide levels by each of 3 different interventions-pretreatment with superoxide dismutase (SOD), diphenylene iodinium (DPI), or knockdown of NADPH oxidase 4 (NOX4) by siRNA-attenuated palmitate-mediated NF-B signaling. Inhibition of toll like receptor-4 (TLR4) signaling also suppressed palmitate-mediated superoxide production and associated inflammation, whereas palmitatemediated superoxide production was not affected by overexpression of a phosphorylation mutant IB␣ (NF-B super repressor) that blocks cellular inflammation downstream of IKK␤/NF-B. Finally, high-fat feeding increased expression of NOX4 and an upstream activator, bone morphogenic protein (BMP4), in thoracic aortic tissue from C57BL/6 mice, but not in TLR4 Ϫ/Ϫ mice, compared to low-fat fed controls. S aturated FFAs such as palmitate readily induce endothelial inflammation, including increased IKK␤-NF-B signaling, via a mechanism that involves activation of Toll-like receptors (TLR) that are key components of the innate immune system. Among the consequences of TLR4-induced activation of NF-B is impaired vascular insulin signaling and reduced nitric oxide production. 1 Based on these and other observations, elevated circulating concentrations of saturated free fatty acids (FFA) are implicated in the mechanism underlying obesity-associated inflammation and insulin resistance in endothelial cells, but the mechanism underlying this link has yet to be established. Conclusions-TheseOne potential mechanism whereby exposure to saturated FFA induces cellular inflammation is via reactive oxygen species (ROS) such as superoxide (O 2 ⅐Ϫ ) 2 that can be generated by both mitochondrial electron transport and by cytosolic enzymes such as the NOX family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. These enzymes transfer electrons from NADPH across cell membranes and are a major source of cytoplasmic ROS. The electron acceptor for this reaction is oxygen, producing superoxide radicals. Of 7 NOX homologues that have been identified in nonphagocytic cells, NOX4 is the major species expressed in endothelial cells, with NOX1, NOX2, and NOX5 being expressed at much lower levels. In vascular tissues of db/db mice, a genetic model of severe obesity and diabetes attributable to a mutation in the leptin receptor, expression of NOX1, NOX4, and p22 phox (a smaller subun...