Choosing to view morbid information involves reward circuitry.

People often seek out stories, videos or images that detail death, violence or harm. Considering the ubiquity of this behavior, it is surprising that we know very little about the neural circuits involved in choosing negative information. Using fMRI, the present study shows that choosing intensely negative stimuli engages similar brain regions as those that support extrinsic incentives and "regular" curiosity.

Effect of collagen turnover and matrix metalloproteinase activity on healing of venous leg ulcers.

Background: The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and normal skin.

Methods: Biopsies were taken from the ulcers of 12 patients whose venous ulcers went on to heal and 15 patients whose ulcers failed to heal despite 12 months of compression bandaging.

Increased collagen degradation around loosened total hip replacement implants.

Objective: To assess collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants.

Methods: The medical indication for the primary total hip replacement was osteoarthritis in all study patients. Samples from the study patients were compared with control synovial membranes obtained from trauma (hip fracture) patients.

MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis.

Objective: To determine protein and activity levels of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) in synovial fluid of patients with knee joint injury, primary osteoarthritis, and acute pyrophosphate arthritis (pseudogout).

Methods: Measurements were done on knee synovial fluid obtained in a cross sectional study of cases of injury (n = 283), osteoarthritis (n = 105), and pseudogout (n = 65), and in healthy controls (n = 35). Activity of MMP-1 and MMP-3 in alpha(2) macroglobulin complexes was measured using specific low molecular weight fluorogenic substrates.

MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis.

Objective: To analyse matrix metalloproteinases (MMPs) and tissue inhibitor-1 of MMPs (TIMP-1) levels in the systemic circulation and synovial fluid (SF) of patients with RA and to compare these levels with inflammatory and collagen degradation markers.

Methods: ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/alpha(2)-macroglobulin complexes, and collagen degradation products were measured by sandwich ELISA, activity assays, and HPLC in paired SF and serum samples from 15 patients with RA and 13 with OA.

Results: MMPs were higher in SF of patients with RA than in OA or controls.

Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis.

Objective: Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly. Its etiology is largely unknown, but age is the most prominent risk factor. The current study was designed to test whether accumulation of advanced glycation end products (AGEs), which are known to adversely affect cartilage turnover and mechanical properties, provides a molecular mechanism by which aging contributes to the development of OA.

Active MMPs captured by alpha 2 macroglobulin as a marker of disease activity in rheumatoid arthritis.

Objective: The aim of the present study was to analyze alpha 2 Macroglobulin/MMP (alpha 2M/MMP) complex formation and to investigate whether MMP activity in alpha 2M/MMP complexes in serum can be used as a disease marker in rheumatoid arthritis (RA).

Methods: High and low molecular weight (H/LMW) substrates and inhibitors and size exclusion were used to analyze alpha 2M/MMP complex formation. LMW fluorogenic substrates were used to quantify the level of MMPs in alpha 2M/MMP complexes in the serum of RA patients and healthy controls.

Advanced glycation end product ligands for the receptor for advanced glycation end products: biochemical characterization and formation kinetics.

Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown.

Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis.

Objective: To analyse the relation between systemic levels of pro-MMP-3, -8, and -9 matrix metalloproteinase (MMP) activity in alpha(2) macroglobulin (alpha(2)M)/MMP complexes and the progression of joint destruction in patients with recent onset rheumatoid arthritis (RA).

Methods: 109 patients with RA of recent onset were entered into this longitudinal study. Patients were followed up for two years; clinical data, blood samples, and radiographs were obtained at baseline and at 1 and 2 years.

AGEing and osteoarthritis: a different perspective.

Purpose Of Review: Across the world, osteoarthritis is the most commonly occurring musculoskeletal disease of the elderly, affecting more than 25% of the population older than 60 years of age. By far the single greatest risk factor for the development of osteoarthritis is age, but a mechanism to explain this relation has not yet been identified. If such a mechanism is identified, this potentially also provides a novel target for osteoarthritis therapy.

Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis.

We investigated whether plasma and synovial fluid (SF) samples from patients with rheumatoid arthritis (RA) contained extracellular mitochondrial DNA (mtDNA) or the oxidatively damaged DNA adduct 8-hydroxy-2'-deoxyguanosine (8-oxodG). Moreover, we correlated the laboratory findings of the patients with RA with their levels of mtDNA and 8-oxodG. SF and plasma samples from 54 patients with RA, SF from 30 non-arthritic control subjects, and plasma from 22 healthy volunteers were collected.

Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis.

The hallmark of fibrotic processes is an excessive accumulation of collagen. The deposited collagen shows an increase in pyridinoline cross-links, which are derived from hydroxylated lysine residues within the telopeptides. This change in cross-linking is related to irreversible accumulation of collagen in fibrotic tissues.

No therapeutic effect of plasmin antagonist tranexamic acid in rheumatoid arthritis. A double-blind placebo-controlled pilot study.

Objective: In the present study, the effects of plasmin antagonist tranexamic acid (TEA) on urinary pyridinoline excretion rates were investigated in rheumatoid arthritis (RA) patients.

Methods: The study was set up as a double-blind placebo-controlled pilot study. Ten patients received tranexamic acid and 9 received placebo for 12 weeks.

Identification of disease- and nutrient-related metabolic fingerprints in osteoarthritic Guinea pigs.

Osteoarthritis (OA), one of the most common diseases among the elderly, is characterized by the progressive destruction of joint tissues. Its etiology is largely unclear and no effective disease-modifying treatment is currently available. Metabolic fingerprinting provides a novel tool for the identification of biomarkers.

Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage.

Objective: To determine whether increasing advanced glycation end products (AGEs) in bovine articular cartilage to levels present in aged human cartilage modulates the tensile biomechanical properties of the tissue.

Methods: Adult bovine articular cartilage samples were incubated in a buffer solution with ribose to induce the formation of AGEs or in a control solution. Portions of cartilage samples were assayed for biochemical indices of AGEs and tested to assess their tensile biomechanical properties, including stiffness, strength, and elongation at failure.

A comparative analysis of bone and cartilage metabolism in two strains of guinea-pig with varying degrees of naturally occurring osteoarthritis.

Objective: To evaluate the interaction of bone and cartilage in knee osteoarthritis (OA) pathogenesis in two guinea-pig strains with appreciable differences in bone metabolism.

Design: Two guinea-pig strains were evaluated for their susceptibilities to OA using semi-quantitative histological grading of knee joints and quantification of biomarkers including urinary excretion of hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP) collagen cross-links, serum osteocalcin (OC), and synovial fluid levels of keratan sulfate (KS).

Results: At 12 months of age, Strain 13 guinea-pigs had minimal to mild histological evidence of OA compared to the Hartley strain guinea-pigs.

Molecular markers for osteoarthritis: the road ahead.

Osteoarthritis is a disabling joint disease that is characterized by the progressive destruction of articular cartilage. Diagnosis is based on clinical symptoms in combination with radiography, which is relatively insensitive and provides only an indication of accumulated damage. Alternative methods, such as molecular markers, are therefore needed that can quantitatively, reliably, and sensitively detect osteoarthritic changes in the joints at an early stage of the disease.

Development of biochemical heterogeneity of articular cartilage: influences of age and exercise.

The objective of this study was to document the development of biochemical heterogeneity from birth to maturity in equine articular cartilage, and to test the hypothesis that the amount of exercise during early life may influence this process. Neonatal foals showed no biochemical heterogeneity whatsoever, in contrast to a clear biochemical heterogeneity in mature horses. The process of formation of site differences was almost completed in exercised foals age 5 months, but was delayed in those deprived of exercise.

Steady progression of osteoarthritic features in the canine groove model.

Objective: Recently we described a canine model of osteoarthritis (OA), the groove model with features of OA at 10 weeks after induction, identical to those seen in the canine anterior cruciate ligament transection (ACLT) model. This new model depends on cartilage damage accompanied by transient intensified loading of the affected joint. The present study evaluates this groove model at 20 and 40 weeks after induction, to assess whether the osteoarthritic features progress in time.

Biochemical development of subchondral bone from birth until age eleven months and the influence of physical activity.

Subchondral bone provides structural support to the overlying articular cartilage, and plays an important role in osteochondral diseases. There is growing insight that the mechanical features of bone are related to the biochemistry of the collagen network and the mineral content. In the present study, part of the normal developmental process and the influence of physical activity on biochemical composition of subchondral bone was studied.

The canine 'groove' model, compared with the ACLT model of osteoarthritis.

Objective: The frequently used anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) in the dog, makes use of a permanent trigger (joint instability) for inducing degenerative changes. The present study evaluates a canine model of degenerative cartilage damage, mimicking OA, which is induced without making use of permanent joint instability.

Methods: The articular cartilage of the weight-bearing areas of the femoral condyles in one knee of ten beagle dogs was damaged by making grooves, without damaging the subchondral bone.

Putative role of lysyl hydroxylation and pyridinoline cross-linking during adolescence in the occurrence of osteoarthritis at old age.

Objective: The collagen network in human articular cartilage experiences a large number of stress cycles during life as it shows hardly any turnover after adolescence. We hypothesized that, to withstand fatigue failure, the physical condition of the collagen network laid down at adolescence is of crucial importance for the age of onset of osteoarthritis (OA).

Methods: We have compared the lysyl hydroxylation level and pyridinoline cross-link level of the collagen network of degenerated (DG) cartilage of the femoral knee condyle (representing a preclinical early stage of OA) with that of normal cartilage from the contralateral knee.

Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage.

Objective: The prevalence of osteoarthritis (OAs) increases with age and coincides with the accumulation of advanced glycation endproducts (AGEs) in articular cartilage, suggesting that accumulation of glycation products may be involved in the development of OA. This study was designed to examine the effects of accumulation of AGEs on the turnover of the extracellular matrix of human articular cartilage.

Design: Chondrocyte mediated cartilage degradation (GAG release, colorimetric) was measured in human articular cartilage of donors aged 19-82 years (N=30, 4-day culture).

Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis.

Objective: Age is an important risk factor for osteoarthritis (OA). During aging, nonenzymatic glycation results in the accumulation of advanced glycation end products (AGEs) in cartilage collagen. We studied the effect of AGE crosslinking on the stiffness of the collagen network in human articular cartilage.

The role of collagen in determining bone mechanical properties.

The hypothesis of this study was that collagen denaturation would lead to a significant decrease in the toughness of bone, but has little effect on the stiffness of bone. Using a heating model, effects of collagen denaturation on the biomechanical properties of human cadaveric bone were examined. Prior to testing, bone specimens were heat treated at varied temperatures (37-200 degrees C) to induce different degrees of collagen denaturation.