IgM and IgG significant reactivity to Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii among Italian patients affected by Lyme arthritis or neuroborreliosis

Abstract This survey evaluates the specificity of band patterns in immunoblot of sera taken from clinically defined cases of Lyme arthritis and neuroborreliosis, towards three locally isolated strains of Borrelia burgdorferi , belonging to the three species: Borrelia sensu stricto, Borrelia garinii and Borrelia afzelii . To assess specificity, patient sera were statistically ( χ ², P ≤ 0.05) compared with blood donors sera samples. Both IgG and IgM antibodies were considered. The overall reactivity of the three Borrelia strains in IgG immunoblots indicated that ten protein bands were significant, with a different prevalence of some of them in the two groups of patient sera: bands at 60-58, 30–33, 36–37 and 28-27 kDa were markers for neuroborreliosis sera; proteins at 100-83, 72-70 and 18-17 kDa behaved like markers for Lyme arthritis. The IgM Immunoblots revealed significant bands at 100-83, 72-70, 51, 24-21 and 18-17 kDa only with neuroborreliosis sera. Though there were variable band reactivities in each strain, a correlation emerged between the three genospecies and the clinical symptoms: in fact B. afzelii and B. garinii were prevalent in Lyme arthritis sera, (IgG Immunoblots); B. garinii was associated to neuroborreliosis (IgG and IgM Immunoblots); B. sensu stricto was strongly reactive with neuroborreliosis in IgM immunoblots. These data indicate that the three locally isolated strains of Borrelia representing the three genospecies should be used together in immunoblot to detect antibodies elicited in neuroborreliosis and Lyme arthritis.     

The role of cyclic-3′,5′-adenosine monophosphate in prostaglandin-mediated inhibition of basic calcium phosphate crystal-induced mitogenesis and collagenase induction in cultured human fibroblasts

Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathies characterised by synovial proliferation and non-inflammatory degradation of intra-articular collagenous structures. BCP crystals stimulate fibroblast and chondrocyte mitogenesis, metalloprotease secretion and prostaglandin production. As a tissue protective effect of prostaglandins has been suggested, we recently studied the effect of PGE₁ on BCP crystal-induced mitogenesis and collagenase mRNA accumulation in human fibroblasts (HF). We demonstrated a dose-dependent inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation. The mechanism of PGE₁ inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation was therefore explored. PGE₁ (100 ng/ml) increased HF intracellular cAMP 40-fold over control. BCP alone caused no such change but inhibited the PGE₁-induced increase in intracellular cAMP by at least 60%. The PGE₁-induced increase in intracellular cAMP was also blocked by the adenyl cyclase inhibitor, 2′,5′-dideoxyadenosine (ddA) (10 μM) and ddA reversed the PGE₁-mediated inhibition of BCP crystal-induced mitogenesis. Dibutyrul cAMP also inhibited BCP crystal-induced mitogenesis in a concentration-dependent manner. Agents which increase intracellular cAMP levels such as the adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effect of PGE₁ on HF collagenase mRNA levels. PGE₁ inhibits the biologic effects of BCP crystals through the cAMP signal transduction pathway and such inhibition may have significant therapeutic implications.     

The effects of total ankle arthroplasty on postural stability and loading symmetry in quiet stance

Ankle osteoarthritis is a debilitating condition affecting about 1% of the population with approximately 50,000 new instances annually. One treatment is total ankle arthroplasty (TAA), however, its effects on balance are not well understood. This study analyzed balance over a two-year period following TAA. 408 subjects (177 left, 231 right ankles) diagnosed with end-stage ankle osteoarthritis performed quiet standing trials while center of pressure (COP) data were collected. Data were compared across three time points (pre-op, 1-year, and 2-years post-op) and between surgical and non-surgical limbs using a linear mixed model with significance set at P = 0.05. COP excursions in the feet-together condition were not significantly different between limbs after 2 years in anteroposterior or mediolateral directions (P = 0.06, 0.08) after being significantly different between limbs in the anteroposterior (P = 0.014) and mediolateral direction (P < 0.001) pre-op. The vertical ground reaction force significantly decreased across time in the non-surgical limb, while reciprocally increasing in the surgical limb (P < 0.001). After 2 years, no significant difference in vertical ground reaction force between limbs existed (P = 0.20). Limb asymmetry indices decreased at each time point in both conditions (all P < 0.001) and were not significantly different from zero after 2 years in the feet-together condition (P = 0.290). In conclusion, surgical limb balance improved compared to pre-op, resulting in increased symmetry between limbs after 2 years. Vertical ground reaction forces on both limbs converge and limb asymmetry indices approach zero two years post-op. Differences in the COP excursion-loading symmetry relationship between limbs could be useful for identifying instability in other pathologies.     

Measurement of local diffusion and composition in degraded articular cartilage reveals the unique role of surface structure in controlling macromolecular transport

Developing effective therapeutics for osteoarthritis (OA) necessitates that such molecules can reach and target chondrocytes within articular cartilage. However, predicting how well very large therapeutic molecules diffuse through cartilage is often difficult, and the relationship between local transport mechanics for these molecules and tissue heterogeneities in the tissue is still unclear. In this study, a 150 kDa antibody diffused through the articular surface of healthy and enzymatically degraded cartilage, which enabled the calculation of local diffusion mechanics in tissue with large compositional variations. Local cartilage composition and structure was quantified with Fourier transform infrared (FTIR) spectroscopy and second harmonic generation (SHG) imaging techniques. Overall, both local concentrations of aggrecan and collagen were correlated to local diffusivities for both healthy and surface-degraded samples (0.3 > R² < 0.9). However, samples that underwent surface degradation by collagenase exhibited stronger correlations (R² > 0.75) compared to healthy samples (R² < 0.46), suggesting that the highly aligned collagen at the surface of cartilage acts as a barrier to macromolecular transport.