Iron and atherosclerosis: Lessons learned from rabbits relevant to human disease.

The role of iron in promoting atherosclerosis, and hence the cardiovascular, neurodegenerative and other diseases that result from atherosclerosis, has been fiercely controversial. Many studies have been carried out on various rodent models of atherosclerosis, especially on apoE-knockout (apoE) mice, which develop atherosclerosis more readily than normal mice. These apoE mouse studies generally support a role for iron in atherosclerosis development, although there are conflicting results.

Quantifying nanodiamonds biodistribution in whole cells with correlative iono-nanoscopy.

Correlative imaging and quantification of intracellular nanoparticles with the underlying ultrastructure is crucial for understanding cell-nanoparticle interactions in biological research. However, correlative nanoscale imaging of whole cells still remains a daunting challenge. Here, we report a straightforward nanoscopic approach for whole-cell correlative imaging, by simultaneous ionoluminescence and ultrastructure mapping implemented with a highly focused beam of alpha particles.

Subwavelength imaging through ion-beam-induced upconversion.

The combination of an optical microscope and a luminescent probe plays a pivotal role in biological imaging because it allows for probing subcellular structures. However, the optical resolutions are largely constrained by Abbe's diffraction limit, and the common dye probes often suffer from photobleaching. Here we present a new method for subwavelength imaging by combining lanthanide-doped upconversion nanocrystals with the ionoluminescence imaging technique.

High-resolution 3D imaging and quantification of gold nanoparticles in a whole cell using scanning transmission ion microscopy.

Increasing interest in the use of nanoparticles (NPs) to elucidate the function of nanometer-sized assemblies of macromolecules and organelles within cells, and to develop biomedical applications such as drug delivery, labeling, diagnostic sensing, and heat treatment of cancer cells has prompted investigations into novel techniques that can image NPs within whole cells and tissue at high resolution. Using fast ions focused to nanodimensions, we show that gold NPs (AuNPs) inside whole cells can be imaged at high resolution, and the precise location of the particles and the number of particles can be quantified. High-resolution density information of the cell can be generated using scanning transmission ion microscopy, enhanced contrast for AuNPs can be achieved using forward scattering transmission ion microscopy, and depth information can be generated from elastically backscattered ions (Rutherford backscattering spectrometry).

Consequences of a fat diet in the distribution of minerals within pancreatic tissues of rats and rabbits.

The effects of plasma lipid overload on pancreatic islet function and on mineral imbalance are issues under debate. However, the outcomes may be biased by the different metabolisms of different species. This prospective study evaluated whether a high fat diet intake changed the distribution of physiologically relevant elements within pancreatic endocrine and exocrine tissues of Sprague Dawley rats and New Zealand White rabbits.

Does iron inhibit calcification during atherosclerosis?

Oxidative stress has been implicated in the etiology of atherosclerosis and even held responsible for plaque calcification. Transition metals such as iron aggravate oxidative stress. To understand the relation between calcium and iron in atherosclerotic lesions, a sensitive technique is required that is quantitatively accurate and avoids isolation of plaques or staining/fixing tissue, because these processes introduce contaminants and redistribute elements within the tissue.

A new technology for revealing the flow profile in integrated lab-on-a-chip.

Purpose: Recently, greater attention has been paid to interactions between biomolecules particularly at the single-molecular level. Due to their novel properties, integrated lab-on-a-chip (LOC) devices and fluorescence correlation spectroscopy (FCS) are in high demand.

Methods: The LOC was manufactured using the technique of proton beam writing.

Zinc supplementation prevents cardiomyocyte apoptosis and congenital heart defects in embryos of diabetic mice.

Oxidative stress induced by maternal diabetes plays an important role in the development of cardiac malformations. Zinc (Zn) supplementation of animals and humans has been shown to ameliorate oxidative stress induced by diabetic cardiomyopathy. However, the role of Zn in the prevention of oxidative stress induced by diabetic cardiac embryopathy remains unknown.

Quantitative analysis of zinc in rat hippocampal mossy fibers by nuclear microscopy.

Zinc (Zn) is involved in regulating mental and motor functions of the brain. Previous approaches have determined Zn content in the brain using semi-quantitative histological methods. We present here an alternative approach to map and quantify Zn levels in the synapses from mossy fibers to CA3 region of the hippocampus.

Carboxylate microsphere-induced cellular toxicity in human lung fibroblasts.

Carboxylate microspheres (CMs) are mainly used in industrial, biomedical and various household products. In this study, we assessed the cytotoxic effects of CMs on human MRC-5 lung fibroblasts by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Oxidative stress was determined by measurements of reactive oxygen species and antioxidant (superoxide dismutase and catalase) levels and proinflammatory cytokines quantified by enzyme-linked immunosorbent assay.

Whole-cell imaging at nanometer resolutions using fast and slow focused helium ions.

Observations of the interior structure of cells and subcellular organelles are important steps in unraveling organelle functions. Microscopy using helium ions can play a major role in both surface and subcellular imaging because it can provide subnanometer resolutions at the cell surface for slow helium ions, and fast helium ions can penetrate cells without a significant loss of resolution. Slow (e.

Nuclear microscopy: a novel technique for quantitative imaging of gadolinium distribution within tissue sections.

All clinically-approved and many novel gadolinium (Gd)-based contrast agents used to enhance signal intensity in magnetic resonance imaging (MRI) are optically silent. To verify MRI results, a "gold standard" that can map and quantify Gd down to the parts per million (ppm) levels is required. Nuclear microscopy is a relatively new technique that has this capability and is composed of a combination of three ion beam techniques: scanning transmission ion microscopy, Rutherford backscattering spectrometry, and particle induced X-ray emission used in conjunction with a high energy proton microprobe.

A novel approach to the identification and quantitative elemental analysis of amyloid deposits--insights into the pathology of Alzheimer's disease.

There is considerable interest in the role of metals such as iron, copper, and zinc in amyloid plaque formation in Alzheimer's disease. However to convincingly establish their presence in plaques in vivo, a sensitive technique is required that is both quantitatively accurate and avoids isolation of plaques or staining/fixing brain tissue, since these processes introduce contaminants and redistribute elements within the tissue. Combining the three ion beam techniques of scanning transmission ion microscopy, Rutherford back scattering spectrometry and particle induced X-ray emission in conjunction with a high energy (MeV) proton microprobe we have imaged plaques in freeze-dried unstained brain sections from CRND-8 mice, and simultaneously quantified iron, copper, and zinc.

WITHDRAWN: Measurement of beam focus quality in biomedical nuclear microscopy.

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Polymer-based microfluidics with surface-enhanced Raman-spectroscopy-active periodic metal nanostructures for biofluid analysis.

The use of microfluidics for biofluid analysis offers a cheaper alternative to conventional techniques in disease diagnosis. However, traditional microfluidics design may be complicated by the need to incorporate separation elements into the system in order to facilitate specific molecular detection. Alternatively, an optical technique known as surface-enhanced Raman spectroscopy (SERS) may be used to enable identification of analyte molecules directly from a complex sample.

Investigation into a surface plasmon related heating effect in surface enhanced Raman spectroscopy.

The irreversible loss of surface enhanced Raman spectroscopy (SERS) intensity derived from electrostatically immobilized Au colloidal substrate is studied. The total intensity of the SERS scattering from crystal violet molecules adsorbed onto the substrate was monitored for up to 240 s under continuous laser irradiation. The rate of signal decay was found to depend upon the thickness of the liquid layer over the coated substrate.

Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet.

Developing atherosclerotic lesions in hypercholesterolemic rabbits are depleted in zinc, while iron accumulates. This study examined the influence of zinc supplementation on the development of atherosclerosis and used isotope dilution gas chromatography-mass spectrometry techniques to measure biomarkers of oxidative lipid damage in atherosclerotic rabbit aorta. Our previous method for F(2)-isoprostane measurement was adapted to include the quantitation of cholesterol oxidation products in the same sample.

Promotion of atherogenesis by copper or iron--which is more likely?

Iron levels increase in atherosclerotic lesions in cholesterol fed-rabbits and play a role in atherosclerosis. We investigated whether copper also rises. Male New Zealand White rabbits were fed high-cholesterol diets for 8 weeks.

Zinc supplementation decreases the development of atherosclerosis in rabbits.

Developing atherosclerotic plaques in cholesterol-fed rabbits are enriched in iron but depleted in zinc. In order to examine further the role of zinc, New Zealand White rabbits were fed a high-cholesterol 1% (w/w) diet with zinc (1 g/kg) supplementation for 8 weeks. After the 8-week period, the average atherosclerotic lesion cross-sectional areas in the aortas of the animals fed with the zinc supplement were significantly decreased (1.

Proton beam writing of three-dimensional nanostructures in hydrogen silsesquioxane.

Proton beam writing (p-beam writing) is a promising new direct-write lithographic technique for three-dimensional nanofabrication. In p-beam writing a megaelectronvolt proton beam is focused to a sub-100-nm spot size and scanned over a suitable resist material. Unlike electrons, when a proton beam interacts with resist it follows an almost straight path resulting in high aspect ratio structures with vertical, smooth sidewalls.

Selenium and mercury are redistributed to the brain during viral infection in mice.

As part of the general host response to coxsackievirus B3 (CB3) infection, the concentration of essential and nonessential trace elements changes in different target organs of the infection. Essential (e.g.

Hypericin-photodynamic therapy (PDT) using an alternative treatment regime suitable for multi-fraction PDT.

Photodynamic therapy (PDT) outcome depends on the conditions under which it is carried out. Maintaining the tumour tissue oxygen level is important for PDT efficacy and using a low fluence rate can improve outcome. In this work we studied the response of human nasopharyngeal carcinoma tumours in murine models to hypericin-PDT carried out under low fluence and fluence rate.

The iron chelator desferrioxamine inhibits atherosclerotic lesion development and decreases lesion iron concentrations in the cholesterol-fed rabbit.

Several epidemiological studies have suggested that increased iron stores are associated with increased atherosclerotic events. In order to test the hypothesis that decreasing the vascular level of iron slows lesion growth, we examined the effects of the iron chelator Desferal (72 mg/kg/day, 5 days/week) on atherosclerosis and lesion iron content in cholesterol-fed New Zealand White rabbits. Rabbits were fed with a 1% w/w cholesterol diet for either 8 weeks (and for the last 5 weeks injected daily with Desferal) or 12 weeks (and for the last 9 weeks injected with Desferal).

The mutual diffusion coefficient for (meth)acrylate monomers as determined with a nuclear microprobe.

The value of the mutual diffusion coefficient DV of two acrylic monomers is determined with nuclear microprobe measurements on a set of polymer films. These films have been prepared by allowing the monomers to diffuse into each other for a certain time and subsequently applying fast ultraviolet photo-polymerization, which freezes the concentration profile. The monomer diffusion profiles are studied with a scanning 2.

Increased iron staining in the cerebral cortex of cholesterol fed rabbits.

The link between hypercholesterolemia and neuronal damage is not clear. In the present study, we studied some of the possible effects of hypercholesterolemia on the brain, using the cholesterol fed New Zealand White rabbit as a model. An increase in the number of iron positive cells (i.