The experiments reported herein are the first MRI investigations of the orientational dependence of T 2 relaxation in articular cartilage at microscopic resolution over the 360°an-gular space. For each of six canine cartilage specimens, 48 independent T 2 -weighted proton images were acquired for 12 different specimen orientations. Pixel-wise monoexponential fits of these proton images produced 12 T 2 relaxation images, each with an in-plane pixel resolution of 13.7 m. Cartilage T 2 as a function of specimen orientation was shown to follow approximately the angular dependence of the nuclear dipoledipole interaction, with local maxima at approximately 55°, 125°, 235°, and 305°. However, the relative amplitudes of the T 2 maxima deviated somewhat from those expected from the dipolar interaction. The amplitudes of these maxima also varied with tissue depth: the largest amplitudes were found in the radial zone, intermediate amplitudes were found in the superficial zone, and there was a continuous decrease in amplitude approaching the transitional zone from the superficial zone above and the radial zone below. We explain the discrepancy between the observed T 2 anisotropy and the angular dependence of the dipolar interaction by means of a simple model which considers the average of one isotropic and two anisotropic spin populations-the first being associated with "free" water, and the latter two arising from collagen-associated waters. We show that even for the "long" T 2 components, which arise in multiplecompartment studies of collagen-water systems, there appears to be two subpopulations. Each has the same peak value of T 2 , but the angular dependence of one is shifted in phase by 90°r Articular cartilage is the thin covering layer at the ends of the bones in a joint, which acts as a load-bearing medium to absorb shocks and distribute stress. In degenerative diseases, such as osteoarthritis, it can lose its functional integrity. Because of the lack of specific and sensitive markers to detect subtle changes in the tissue, there have been no clinical methods for nondestructively assessing the functional, structural, and biochemical properties of articular cartilage, especially at the early stages of osteoarthritis. The difficulty is mainly due to the curved geometry of articular cartilage and the fact that its molecular composition and organization vary along its (thin) depth. This depth-dependent ultrastructure is essentially defined by the organization of the collagen fibrils, which is shown in histology to have three predominant organizational zones across the depth of the noncalcified tissue. Starting from the surface, these three zones are: 1) the superficial (tangential) zone, where the fibrils are parallel to the surface; 2) the transitional (intermediate) zone, where the fibrils are mostly randomly oriented; and 3) the radial (deep) zone, where the fibrils are oriented perpendicular to the surface (1-3). Tissue with such highly organized and heterogeneous structures can exhibit different properties when mea...

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Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2–50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level.

We studied the structural and antimicrobial properties of copper oxide nanoparticles (CuO NPs) synthesized by a very simple precipitation technique. Copper (II) acetate was used as a precursor and sodium hydroxide as a reducing agent. X-ray diffraction patter (XRD) pattern showed the crystalline nature of CuO NPs. Field emission scanning electron microscope (FESEM) and field emission transmission electron microscope (FETEM) demonstrated the morphology of CuO NPs. The average diameter of CuO NPs calculated by TEM and XRD was around 23 nm. Energy dispersive X-ray spectroscopy (EDS) spectrum and XRD pattern suggested that prepared CuO NPs were highly pure. CuO NPs showed excellent antimicrobial activity against various bacterial strains (Escherichia coli,Pseudomonas aeruginosa,Klebsiella pneumonia,Enterococcus faecalis,Shigella flexneri,Salmonella typhimurium,Proteus vulgaris,andStaphylococcus aureus). Moreover,E. coliandE. faecalisexhibited the highest sensitivity to CuO NPs whileK. pneumoniawas the least sensitive. Possible mechanisms of antimicrobial activity of CuO NPs should be further investigated.

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Objectives: To detect changes in the collagen fibril network in articular cartilage in a canine experimental model of early osteoarthritis (OA) using microscopic magnetic resonance imaging (mMRI) and polarised light microscopy (PLM). Methods: Eighteen specimens from three pairs of the medial tibia of an anterior cruciate ligament transection canine model were subjected to mMRI and PLM study 12 weeks after surgery. For each specimen, the following experiments were carried out: (a) two dimensional mMRI images of T 2 relaxation at four orientations; (b) the tangent Young's modulus; and (c) two dimensional PLM images of optical retardance and fibril angle. Disease induced changes in tissue were examined across the depth of the cartilage at a mMRI resolution of 13.7-23.1 mm. Results: Several distinct changes from T 2 weighted images of cartilage in OA tibia were seen. For the specimens that were covered at least in part by the meniscus, the significant changes in mMRI included a clear shift in the depth of maximum T 2 (21-36%), a decrease in the superficial zone thickness (37-38%), and an increase in cartilage total thickness (15-27%). These mMRI changes varied topographically in the tibia surface because they were not significant in completely exposed locations in medial tibia. The mMRI results were confirmed by the PLM measurements and correlated well with the mechanical measurements. Conclusion: Both mMRI and PLM can detect quantitatively changes in collagen fibre architecture in early OA and resolve topographical variations in cartilage microstructure of canine tibia.

Purpose: To characterize a number of physical and morphologic properties of young articular cartilage. These properties include the anisotropy of T 2 relaxation, optical retardation, orientation of the collagen fibrils, total thickness of the tissue, number of histologic sub-zones in the tissue, width of individual sub-zones, and correlation between the depths of the local T 2 maxima and the local retardation minima. Materials and Methods:Microscopic magnetic resonance imaging ( MRI) and polarized light microscopy (PLM) were used to examine three side-by-side specimens from a humeral head of a three-month-old beagle that exhibited a unique topographic heterogeneity from three-zones centrally to multi-zone peripherally. Results:The centrally located specimen showed that the collagen fibrils across the tissue depth have a pattern of the classic three histologic sub-zones (tangential, transitional, and radial). A much more complicated multi-zone structure was found in the specimen located peripherally, with a second transitional zone and a second tangential zone located at the deep part of the tissue. We also showed that the orientation of the collagen fibrils that form the cocoonshaped territorial matrix surrounding the clusters of chondrocytes can be imaged by our PLM technique. Conclusion:The results from the young animal in this report, together with our observations from older animals, demonstrate that MRI and PLM can be used to study the epiphyseal expansion of cartilage in young animals during its growth and subsequent loss in older animals. An illustrative model for the structure of collagen fibrils in a humeral head is suggested as an extension to the classic three-zone model for young articular cartilage.

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