Glycosaminoglycans (GAGs) are the main source of tissue fixed charge density (FCD) in cartilage, and are lost early in arthritic diseases. We tested the hypothesis that, like Na+, the charged contrast agent Gd-DTPA2- (and hence proton T1) could be used to measure tissue FCD and hence GAG concentration. NMR spectroscopy studies of cartilage explants demonstrated that there was a strong correlation (r > 0.96) between proton T1 in the presence of Gd-DTPA2- and tissue sodium and GAG concentrations. An ideal one-compartment electrochemical (Donnan) equilibrium model was examined as a means of quantifying FCD from Gd-DTPA2- concentration, yielding a value 50% less but linearly correlated with the validated method of quantifying FCD from Na+. These data could be used as the basis of an empirical model with which to quantify FCD from Gd-DTPA2- concentration, or a more sophisticated physical model could be developed. Spatial distributions of FCD were easily observed in T1-weighted MRI studies of trypsin and interleukin-1 induced cartilage degradation, with good histological correlation. Therefore, equilibration of the tissue in Gd-DTPA2- gives us the opportunity to directly image (through T1 weighting) the concentration of GAG, a major and critically important macromolecule in cartilage. Pilot clinical studies demonstrated Gd-DTPA2- penetration into cartilage, suggesting that this technique is clinically feasible.

Despite the compelling need mandated by the prevalence and morbidity of degenerative cartilage diseases, it is extremely difficult to study disease progression and therapeutic efficacy, either in vitro or in vivo (clinically). This is partly because no techniques have been available for nondestructively visualizing the distribution of functionally important macromolecules in living cartilage. Here we describe and validate a technique to image the glycosaminoglycan concentration (

Cancer chemotherapy resistance (MDR) is the innate and/or acquired ability of cancer cells to evade the effects of chemotherapeutics and is one of the most pressing major dilemmas in cancer therapy. Chemotherapy resistance can arise due to several host or tumor-related factors. However, most current research is focused on tumor-specific factors and specifically genes that handle expression of pumps that efflux accumulated drugs inside malignantly transformed types of cells. In this work, we suggest a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer.

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Cartilage degenerative diseases affect millions of people. Our understanding of these diseases and our ability to establish efficacious treatment strategies have been confounded by the difficulty of nondestructively evaluating the state of cartilage. Imaging strategies that allow visualization of cartilage integrity would revolutionize the field by allowing us to visualize early stages of degeneration and thus to evaluate predisposing factors for cartilage disease and changes resulting from interventions (eg, therapies) in culture studies, tissue-engineered systems, animal models, and in vivo in humans. Here we briefly review current state-of-the-art MRI strategies relevant to understanding and following treatment in early cartilage degeneration. We review MRI as applied to the assessment of the whole joint, of cartilage as a whole (as an organ), of cartilage tissue, and of cartilage molecular composition and structure. Each of these levels is amenable to assessment by MRI and offers different information that, in the long run, will serve as an important element of cartilage imaging.

The most common MR-based approach to noninvasively measure brain temperature relies on the linear relationship between the 1 H MR resonance frequency of tissue water and the tissue's temperature. Herein we provide the most accurate in vivo assessment existing thus far of such a relationship. It was derived by acquiring in vivo MR spectra from a rat brain using a high field (11.74 Tesla [T]) MRI scanner and a single-voxel MR spectroscopy technique based on a LASER pulse sequence. Data were analyzed using three different methods to estimate the 1 H resonance frequencies of water and the metabolites NAA, Cho, and Cr, which are used as temperature-independent internal (frequency) references. Standard modeling of frequency-domain data as composed of resonances characterized by Lorentzian line shapes gave the tightest resonance-frequency versus temperature correlation. An analysis of the uncertainty in temperature estimation has shown that the major limiting factor is an error in estimating the metabolite frequency. Proton ( 1 H) MRS thermometry provides a unique noninvasive method to monitor changes in brain temperature or to quantify absolute brain temperature. The MR frequency of water protons depends on temperature, and it changes with a coefficient of approximately Ϫ0.01 ppm/°C (1). It has been shown by means of magnetic resonance imaging (2) and spectroscopy that this approach can be used for in vivo noninvasive temperature mapping (3) and tracking of changes in tissue temperature during functional activation (4). The possibility to quantify absolute brain temperature by monitoring the difference between the water resonance frequency and a temperature independent metabolite resonance frequency (internal reference) has also been demonstrated (5,6).The 1 H resonance of the N-acetyl-aspartate (NAA) methyl group is most often used to provide a temperature independent internal reference frequency for in vivo temperature quantification in brain tissue due to the relatively high concentration of NAA as compared to other metabolites (5-11). However, because of the small temperature/ water-chemical-shift correlation coefficient and low NAA signal amplitude (NAA concentration in the normal brain tissue is approximately 10,000 times smaller than the water concentration) the accuracy of the method is limited. Two major factors define this accuracy: (i) the predetermined temperature versus 1 H MR water frequency correlation (ϳ Ϫ0.01 ppm/°C) and (ii) the accuracy in estimating the internal reference (metabolite) 1 H resonance frequency. Existing literature data suggest there is substantial room for improvement in obtaining a more accurate, internally referenced, calibration curve. This topic is the principal focus of this study. MATERIALS AND METHODS Animal PreparationMale Sprague Dawley rats (n ϭ 3) weighing ϳ300 -400 g were initially anesthetized with a ketamine/xylazine combination anesthesia (72.9 mg/kg and 10.4 mg/kg, respectively) and given time to stabilize. The animals were then restrained in a prone position within a...

The GAG level in grafts that were implanted for less than 12 months appeared to be lower than that in the remote cartilage. At 12 months or greater, the grafts in this study had GAG levels that were comparable to both the adjacent and remote cartilage. This preliminary study of ACT implants has shown that it is feasible to apply the dGEMRIC technique in patients with ACT as a way to obtain information related to the composition of grafts. These results provide motivation and the pilot data with which to design further clinical studies.

Helicobacter pylori (HP) is a facultative anaerobic bacterium. HP is a normal flora having immuno-modulating properties. This bacterium is an example of a microorganism inducing gastric cancer. Its carcinogenicity depends on bacteria-host related factors. The proper understanding of the biology of HP inducing gastric cancer offers the potential strategy in the managing of HP rather than eradicating it. In this article, we try to summarize the biology of HP-induced gastric cancer and discuss the current pharmacological approach to treat and prevent its carcinogenicity.