Biomedical subjects

Sonya Shortkroff

Publications and source records attributed to Sonya Shortkroff.

6 recordsLinked to original sources

PubMed2006

Optimized extraction of glycosaminoglycans from normal and osteoarthritic cartilage for glycomics profiling.

Articular cartilage is a highly specialized smooth connective tissue whose proper functioning depends on the maintenance of an extracellular matrix consisting of an integrated assembly of collagens, glycoproteins, proteoglycans (PG), and glycosaminoglycans. Isomeric chondroitin sulfate glycoforms differing in position and degree of sulfation and uronic acid epimerization play specific and distinct functional roles during development and disease onset. This work introduces a novel glycosaminoglycan extraction method for the quantification of mixtures of chondroitin sulfate oligosaccharides from intact cartilage tissue for mass spectral analysis. Glycosaminoglycans were extracted from intact cartilage samples using a combination of ethanol precipitation and enzymatic release followed by reversed-phase and strong anion exchange solid-phase extraction steps. Extracted chondroitin sulfate glycosaminoglycans were partially depolymerized using chondroitinases, labeled with 2-anthranilic acid-d(4) (2-AA) and subjected to size exclusion chromatography with online electrospray ionization mass spectrometric detection in the negative ion mode. The method presented herein enabled simultaneous determination of sulfate position and uronic acid epimerization in juvenile bovine and adult human cartilage samples. The method was applied to a series of 13 adult human cartilage explants. Standard deviation of the mean for the measurements was 1.6 on average. Coefficients of variation were approximately 4% for all compositions of 40% or greater. These results show that the new method has sufficient accuracy to allow determination of topographical distribution of glycoforms in connective tissue.

Adult↗

PubMed2006

Assessment of coronary plaque collagen with polarization sensitive optical coherence tomography (PS-OCT).

INTRODUCTION: Current evidence indicates that most plaques classified as vulnerable or ruptured plaque do not lead to unstable angina or myocardial infarction. Improved methods are needed to risk stratify plaques to identify those which lead to most acute coronary syndromes. Collagen depletion in the intima overlying lipid collections appears to be a critical component of unstable plaques. In this study, we use polarization sensitive optical coherence tomography (PS-OCT) for the assessment of coronary plaque collagen. Collagen is birefringent, meaning that different polarization states travel through it at different velocities. METHODS AND RESULTS: Changes in PS-OCT images are a measure of tissue birefringence. Twenty-two coronary artery segments were imaged with PS-OCT and analyzed by picrosirius staining (a measure of collagen intensity and fiber size) and trichrome blue. The regression plot between PS-OCT changes and measured collagen yielded a correlation coefficient value of 0.475 (p<0.002). The predictive value of a PS-OCT measurement of negligible birefringence (less than 33% change) for minimal collagen was 93% while the predictive value of high birefringence (greater than 66% change) for high collagen concentrations was 89%. The effect of fiber type (chemical composition) was minimal relative to the effect due to fiber concentration. CONCLUSION: The capability of PS-OCT to assess plaque collagen content, in addition to its ability to generate high resolution structural assessments, make it a potentially powerful technology for identifying high risk plaques.

Aged↗

PubMed2006

High-resolution imaging of progressive articular cartilage degeneration.

The objective of this study was to develop and verify a new technique for monitoring the progression of osteoarthritis (OA) by combining a rat model with the imaging modality optical coherence tomography (OCT). Time-sequential, in vivo, OCT imaging was performed on the left femoral condyles of 12 Wistar rats following sodium-iodoacetic acid-induced OA progression. The right femoral condyles (untreated) were also imaged and served as controls. Imaging was performed on days 0, 10, 20, 30, and 60 with an OCT system capable of acquiring images at four frames per second and an axial resolution of 5 microm. Progressive changes were analyzed using an OA scoring system. OCT successfully identified progressive cartilage degeneration as well as alteration of the cartilage/bone interface. Significant changes to both of these structures were observed in the sodium-iodoacetic acid-injected condyles. Structural changes detected with OCT were confirmed histologically. OCT in combination with a well-known model used in arthritis research represents a powerful tool for following degenerative joint disease progression in a given animal by detecting changes to the cartilage/bone interface and articular cartilage.

Animals↗

PubMed2005

Wnt influence on chondrocyte differentiation and cartilage function.

The Wnt signaling network regulates chondrocyte differentiation, proliferation, and maturation during embryonic limb development. In this review, we summarize studies of Wnt signaling during the chondrocyte life cycle in avian and mammalian systems, both before and after birth. Recent reports that implicate abnormal Wnt signaling as a contributing factor to pathogenic joint conditions are also discussed. In addition, we show new data that suggests Wnt signaling is active in adult cartilage. Overall, it appears that the Wnt network has dual roles in cartilage, as has been described in other tissues: it is an important regulator of chondrocyte development, but deregulated signaling is detrimental to mature tissues and may lead to disease.

Animals↗

PubMed2004

Dose response of the AIA rabbit stifle joint to boron neutron capture synovectomy.

This study assessed the treatment with boron neutron capture synovectomy of synovitis in the antigen-induced arthritis (AIA) model. A boron compound, potassium dodecahydrododeca-borate (K(2)B(12)H(12)), was injected into stifle joints of 24 AIA and 12 normal rabbits and activated by neutron bombardment of the joint to achieve doses from 800 to 81,000 RBE-cGy. Synovial ablation in the AIA joint was accomplished at doses of 6,000 to 7,000 RBE-cGy with no adverse effects to skin or extracapsular tissues.

Animals↗

PubMed2002

Magnetic resonance relaxivity of dendrimer-linked nitroxides.

The relaxivity and bioreduction rates of eight dendrimer-linked nitroxides varying in the number of nitroxides per molecule were measured and the potential use of these compounds as MR contrast agents was demonstrated. The T(1) and T(2) relaxivities, measured at room temperature and 1.5 T, varied linearly with the number of nitroxides per molecule for compounds with up to 16 nitroxides per molecule. Fourth-generation polypropylenimide- (DAB) and third-generation polyamidoamine- (PAMAM) dendrimer-linked nitroxides were found to have greater relaxivity than gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The greater number of nitroxides per dendrimer increased relaxivity over that of a single nitroxide, allowing a decreased dose to achieve differential contrast with MR evaluations. Rates of nitroxide bioreduction were below detection threshold using EPR spectroscopy for generation 2 dendrimers and higher. A pilot assessment of in vivo cartilage uptake that compared intraarticular injection of three structurally different dendrimer-linked nitroxides with Gd-DTPA and with saline demonstrated high affinity of the DAB-dendrimer-linked nitroxides for normal rabbit articular cartilage. From these results, it is evident that target-specific dendrimer-linked nitroxides can be designed.

Animals↗