Angiogenesis in the pathogenesis of inflammatory joint and lung diseases

This paper reviews hypotheses about roles of angiogenesis in the pathogenesis of inflammatory disease in two organs, the synovial joint and the lung. Neovascularisation is a fundamental process for growth and tissue repair after injury. Nevertheless, it may contribute to a variety of chronic inflammatory diseases, including rheumatoid arthritis, osteoarthritis, asthma, and pulmonary fibrosis. Inflammation can promote angiogenesis, and new vessels may enhance tissue inflammation. Angiogenesis in inflammatory disease may also contribute to tissue growth, disordered tissue perfusion, abnormal ossification, and enhanced responses to normal or pathological stimuli. Angiogenesis inhibitors may reduce inflammation and may also help to restore appropriate tissue structure and functio

Osteochondral angiogenesis and increased protease inhibitor expression in OA

SummaryObjectiveNormal cartilage is resistant to vascular invasion and anti-angiogenic protease inhibitors may contribute to its avascular status. We hypothesized that dysregulated expression of four key anti-angiogenic protease inhibitors may contribute to increased osteochondral vascularity in osteoarthritis (OA).DesignMedial tibial plateaux from OA patients (n=40) were compared with those from non-arthritic controls collected post-mortem (PM, n=10). Immunohistochemistry was performed for protease inhibitors TIMP-1, TIMP-3, PAI-1 and SLPI and the pro-angiogenic factor vascular endothelial growth factor (VEGF). Immunoreactivity in articular chondrocytes was scored. Chondropathy was measured as a modified Mankin score, and osteochondral vascular density as number of channels crossing each mm of tidemark. Non-parametric analyses were used for all data.ResultsAll protease inhibitors and VEGF were localised to chondrocytes near the articular surface, less often in the middle zone, and rarely to deep chondrocytes. Scores for VEGF, TIMP-1, TIMP-3, SLPI and PAI-1 were all increased in OA compared with PM, and higher scores were associated with greater chondropathy. Chondrocyte expression of VEGF was associated with higher osteochondral vascular density (r=0.32, P<0.05), whereas protease inhibitors were not.ConclusionsThe resistance of normal articular cartilage to vascular invasion may be more due to its matrix environment than ongoing protease inhibitor expression. Upregulation of protease inhibitors by superficial chondrocytes in OA may moderate the angiogenic effects of growth factors such as VEGF. However, failure of deep chondrocytes to express anti-angiogenic protease inhibitors may permit vascular invasion into the articular cartilage

Visualisation of the local electrochemical activity of thermally-sprayed anti-corrosion coatings using scanning electrochemical microscopy

Scanning electrochemical microscopy was used to probe the local electrochemical activity of anti-corrosion coatings formed from Inconel 625, a Ni-Cr-Mo alloy commonly used in engineering applications. The coatings were formed using a high velocity oxygen fuel thermal spraying technique. Upon spraying onto mild steel substrates, clear splat boundaries were formed at the interface between droplets of the alloy as they cooled on the substrate surface. Scanning electrochemical microscopy in the feedback mode, employing ferrocenemethanol as redox mediator, was used to determine the local electrochemical activity of samples of the wrought alloy, the sintered alloy and the thermally-sprayed coating. Significantly, the wrought and sintered materials generally showed responses typical of those expected for a purely insulating material. However, feedback approach curve data showed that the electrochemical activity of the entire thermally-sprayed coating was higher than that of the bulk alloy. Local variations in the coating’s activity were then visualised using scanning electrochemical microscopy. These observations indicate that the spraying process increases the conductivity of Inconel 625 and that localised regions of increased electrochemical activity are generated throughout the material, which appear to be related to the splat boundaries formed during spraying

The relationship between different types of dissociation and psychosis-like experiences in a non-clinical sample

This study investigates whether detachment-type dissociation, compartmentalisation-type dissociation or absorption was most strongly associated with psychosis-like experiences in the general population. Healthy participants (N=215) were tested with the Dissociative Experiences Scale (DES, for detachment-related dissociative experiences); the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A, for dissociative compartmentalisation); the Tellegen Absorption Scale (TAS, for non-clinical ‘functional’ dissociative experience); and two measures of psychotic-like experiences, the 21-item Peters et al. Delusions Inventory (PDI-21) and the Cardiff Anomalous Perceptions Scale (CAPS). In multiple regression analyses, DES and TAS but not HGSHS: A scores were found to be significantly associated with PDI-21 and CAPS overall scores. A post-hoc hierarchical cluster analysis checking for cluster overlap between DES and CAPS items, and the TAS and CAPS items showed no overlap between items on the DES and CAPS and minimal overlap between TAS and CAPS items, suggesting the scales measure statistically distinct phenomena. These results show that detachment-type dissociation and absorption, but not compartmentalisation-type dissociation are significantly associated with psychosis-like experiences in a non-clinical population

Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis

SummaryObjectivesWe hypothesised that osteochondral and synovial angiogenesis in osteoarthritis (OA) are independent processes. We investigated whether indices of osteochondral and synovial angiogenesis display different relationships with synovitis, disease severity and chondrocalcinosis in patients with OA.DesignSynovium and medial tibial plateaux were obtained from 62 patients undergoing total knee joint replacement for OA (18 [29%] had chondrocalcinosis) and from 31 recently deceased people with no evidence of joint pathology post-mortem (PM). Vascular endothelium, proliferating endothelial cells (ECs) and macrophages were quantified by immunohistochemistry for CD34, CD31/Ki67 and CD14, respectively. Grades were assigned for radiographic and histological OA disease severity, clinical disease activity and histological synovitis (based on cellular content of the synovium).ResultsBlood vessels breached the tidemark in 60% of patients with OA and 20% of PM controls. Osteochondral vascular density increased with increasing cartilage severity and clinical disease activity scores, but not with synovitis. Synovial EC proliferation, inflammation and macrophage infiltration were higher in OA than in PM controls. Synovial angiogenesis indices increased with increasing histological synovitis, but were not related to osteochondral vascular density or other indices of OA disease severity. OA changes were more severe in patients with concurrent chondrocalcinosis. Chondrocalcinosis was not associated with increased angiogenesis or histological synovitis beyond that seen in OA alone.ConclusionOsteochondral and synovial angiogenesis appear to be independent processes. Osteochondral vascularity is associated with the severity of OA cartilage changes and clinical disease activity, whereas synovial angiogenesis is associated with histological synovitis. Modulation of osteochondral and synovial angiogenesis may differentially affect OA disease

BioMiCo:A supervised Bayesian model for inference of microbial community structure

Here, we describe a novel hierarchical model for Bayesian inference of microbial communities (BioMiCo). The model takes abundance data derived from environmental DNA, and models the composition of each sample by a two-level hierarchy of mixture distributions constrained by Dirichlet priors. BioMiCo is supervised, using known features for samples and appropriate prior constraints to overcome the challenges posed by many variables, sparse data, and large numbers of rare species. The model is trained on a portion of the data, where it learns how assemblages of species are mixed to form communities and how assemblages are related to the known features of each sample. Training yields a model that can predict the features of new samples. We used BioMiCo to build models for three serially sampled datasets and tested their predictive accuracy across different time points. The first model was trained to predict both body site (hand, mouth, and gut) and individual human host. It was able to reliably distinguish these features across different time points. The second was trained on vaginal microbiomes to predict both the Nugent score and individual human host. We found that women having normal and elevated Nugent scores had distinct microbiome structures that persisted over time, with additional structure within women having elevated scores. The third was trained for the purpose of assessing seasonal transitions in a coastal bacterial community. Application of this model to a high-resolution time series permitted us to track the rate and time of community succession and accurately predict known ecosystem-level events

On a stochastic partial differential equation with non-local diffusion

In this paper, we prove existence, uniqueness and regularity for a class of stochastic partial differential equations with a fractional Laplacian driven by a space-time white noise in dimension one. The equation we consider may also include a reaction term