Significance of Elevated Blood Metal Ion Levels in Patients with Metal-on-Metal Prostheses: An Evaluation of Oxidative Stress Markers

It is widely known that cobalt and chromium ions can enhance the production of reactive oxygen species, known to be damaging to cells by disturbing their redox status and then generating oxidative stress. The aim of the present study was to determine if increased metal ion levels induce a state of oxidative stress in patients with metal-on-metal (MM) hip arthroplasty. Results indicated that there was no significant difference in the concentration of oxidative stress markers (total antioxidants, peroxides, and nitrated proteins) in the patients with MM bearings compared to patients without prostheses. The activity antioxidant enzymes was stable (catalase and glutathione peroxidase) or slightly decreased (superoxide dismutase and heme oxygenase-1) over time. This work is the first to determine the biological effects of metal ions released from MM hip implants with regards to mid-term systemic oxidative stress and showed that the increased levels of Co and Cr ions are not associated with significant oxidative stress damage in the plasma of patients with these implants

Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish

The inhibitory extracellular matrix in a spinal lesion site is a major impediment to axonal regeneration in mammals. In contrast, the extracellular matrix in zebrafish allows substantial axon re-growth, leading to recovery of movement. However, little is known about regulation and composition of the growth-promoting extracellular matrix. Here we demonstrate that activity of the Wnt/beta-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/beta-catenin signaling induces expression of col12a1a/b and deposition of Collagen XII, which is necessary for axons to actively navigate the non-neural lesion site environment. Overexpression of col12a1a rescues the effects of Wnt/beta-catenin pathway inhibition and is sufficient to accelerate regeneration. We demonstrate that in a vertebrate of high regenerative capacity, Wnt/beta-catenin signaling controls the composition of the lesion site extracellular matrix and we identify Collagen XII as a promoter of axonal regeneration. These findings imply that the Wnt/beta-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species

Astrocyte scar formation aids central nervous system axon regeneration

Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration

ESTAR Measurements During the Southern Great Plains Experiment (SGP99)

During the Southern Great Plains experiment, the synthetic aperture radiometer, ESTAR, mapped L-band brightness temperature over a swath about 50 km wide and about 300 km long extending west from Oklahoma City to El Reno and north from the Little Washita River watershed to the Kansas border. ESTAR flew on the NASA P-3B Orion aircraft at an altitude of 7.6 km and maps were made on 7 days between July 8-20, 1999. The brightness temperature maps reflect the patterns of soil moisture expected from rainfall and are consistent with values of soil moisture observed at the research sites within the SGP99 study area and with previous measurements in this area. The data add to the resources for hydrologic modeling in this area and are further validation of the technology represented by ESTAR as a potential path to a future mission to map soil moisture globally from space

Multi-Tissue Microarray Analysis Identifies a Molecular Signature of Regeneration

<div><p>The inability to functionally repair tissues that are lost as a consequence of disease or injury remains a significant challenge for regenerative medicine. The molecular and cellular processes involved in complete restoration of tissue architecture and function are expected to be complex and remain largely unknown. Unlike humans, certain salamanders can completely regenerate injured tissues and lost appendages without scar formation. A parsimonious hypothesis would predict that all of these regenerative activities are regulated, at least in part, by a common set of genes. To test this hypothesis and identify genes that might control conserved regenerative processes, we performed a comprehensive microarray analysis of the early regenerative response in five regeneration-competent tissues from the newt <em>Notophthalmus viridescens</em>. Consistent with this hypothesis, we established a molecular signature for regeneration that consists of common genes or gene family members that exhibit dynamic differential regulation during regeneration in multiple tissue types. These genes include members of the matrix metalloproteinase family and its regulators, extracellular matrix components, genes involved in controlling cytoskeleton dynamics, and a variety of immune response factors. Gene Ontology term enrichment analysis validated and supported their functional activities in conserved regenerative processes. Surprisingly, dendrogram clustering and RadViz classification also revealed that each regenerative tissue had its own unique temporal expression profile, pointing to an inherent tissue-specific regenerative gene program. These new findings demand a reconsideration of how we conceptualize regenerative processes and how we devise new strategies for regenerative medicine.</p> </div

Conserved molecular programs support regeneration across multiple tissue types.

<p>Select annotated genes with differential expression during early regeneration were grouped according to their primary <i>in vivo</i> function. Upregulation for at least one time point in the designated tissue is indicated by ▴ (≥2-fold), ▴ (≥5-fold), and ▴ (≥10-fold). Downregulation for at least one time point in the designated tissue is indicated by ▾ (≥2-fold), ▾ (≥5-fold), and ▾(≥10-fold). Up- and down-ward arrowheads in a given tissue column for the same gene indicate changes in expression direction over the investigated time course.</p

Human meniscal proteoglycan metabolism in long-term tissue culture.

For the purpose of human meniscal allografting, menisci have been maintained viable in in vitro culture. The influence of long-term tissue culture on the extracellular matrix metabolism of the meniscus has been studied. Fetal calf serum (FCS) was used as a supplement for the growth factors necessary to maintain optimal meniscal cell metabolism. A series of semilunar cartilage samples was cultured under serum-free conditions since foreign proteins could be responsible for immunological problems after eventual allografting. The proteoglycan metabolism in human menisci cultured in FCS-supplemented and in serum-free culture media was compared. To rule out any influence of topographical variations in glycosaminoglycan (GAG) content on proteoglycan (PG) metabolism, GAG concentrations within the tissue were determined, and sulphate (35S) incorporation was studied in tissue samples with a comparable biochemical composition. Sulphate incorporation was preserved when 20% FCS was added to the nutrient medium. The meniscal tissue fibroblasts continued to produce 35S-PG during 4 weeks of culture. The PG molecules were shown to consist of PG-aggregates, monomers and a low molecular-weight PG population. Newly synthesized GAG consisted of approximately 55% chondroitin 4- and 6-sulphate and 33% dermatan sulphate. In the presence of serum, 35S incorporation in PG and in the PG-aggregate fraction significantly increased during the first 2 weeks and then decreased during the following 2 weeks of in vitro culture. Newly synthesized PG-aggregates were almost entirely accumulated in the tissue during these weeks. In the 3rd week the values for this parameter decreased slightly. 35S-PG synthesis dramatically declined after 4 weeks of in vitro culture. Catabolism probably resulted in increased proportions of 35S-PG in the incubation media. In the absence of serum, 35S-PG production also increased in the 2nd week of culture. However, 35S activity was almost exclusively found in small PG, and this material apparently diffused to the incubation media. Consequently, catabolism is higher, and the immobilization of 35S-PG is poor when FCS is not added to the culture media. Our findings suggest that menisci are maintained in viable condition and may serve for allografting at least during 2 weeks of tissue cultur

Summary statistics for regeneration microarray studies.

<p>Analysis is based on log₁₀ transformed data for all tissue types and time points. Each regulation category represents the entire, inclusive data set with percent values derived from dividing the number of genes in each category by the total 1,860 genes represented on the array. Selected differentially expressed genes correlate to the subset of genes and/or gene families that are specifically discussed in the text.</p