Low molecular weight heparin aggravates infectious arthritis triggered by Staphylococcus aureus.

PURPOSE: Staphylococcus aureus is responsible for the majority of wound infections in clean surgical procedures that involve implantation of foreign material, grafts or prosthetic devices. The aim of the study was to assess the effect of low molecular weight heparin on the development and progression of S. aureus arthritis. MATERIALS AND METHODS: The murine model of hematogenously acquired septic arthritis was used injecting intravenously toxic shock syndrome toxin-1 (TSST-1) producing S. aureus of LS-1 strain. Mice lacking prosthetic implants were treated with intraperitoneal injections of low molecular weight heparin, used routinely as anti-thrombotic prophylaxis following joint prosthetic surgery. Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of low molecular weight heparin on T cell dependent and independent inflammation was assessed. RESULTS: Seven days after inoculation with bacteria 18 out of 19 low molecular weight heparin treated mice displayed clinical symptoms of arthritis as compared to 9 out of 23 control animals (p < 0.05), and the severity of arthritis, expressed as arthritic index, was 2.6+/-0.5 versus 1.6+/-0.5 (p = 0.05). The histopathological examination confirmed the clinical findings showing that both inflammation and joint destruction were more substantial in heparin treated animals. CONCLUSION: Our findings indicate that the routine anti-coagulation treatment with heparin contributes to more severe course of joint infection.     

Microbial superantigens as virulence factors and ways to counteract their actions

Microbial superantigens represent a group of molecules that is able to cause massive activation of the host immune system. Human diseases originating from superantigen-secreting bacterial agents are characterized by shock, which continues to pose major health problems. Presently, the treatment of superantigen-mediated infections is limited to the administration of antibiotics and handling of the state of shock. However, the development of multiple antibiotic-resistant, superantigen-producing bacterial strains increases the threat of these infections, and prompts researchers to better understand and treat disease states in which exposure to superantigens is at least partly responsible for the outcome. In the past decade, significant understanding has been achieved regarding the molecular mechanisms of superantigen-host interactions. Based on this understanding, a variety of promising strategies directed against superantigens have been developed. In this review, we discuss some of these strategies, as well as the potential for therapeutic applications of superantigens for the benefit of the host.     

Aerobic Training Effect on Arterial Stiffness in Metabolic Syndrome

Background

Metabolic syndrome, physical inactivity, and central obesity contribute to early vascular aging, which leads to increased risk of cardiovascular disease. This study aimed to assess the effect of heart rate (HR)-targeted aerobic exercise training on the indices of early vascular aging, in particular, arterial stiffness, and on anthropometric and clinical profile of metabolic syndrome subjects.

Addition of corticosteroids to antibiotic treatment ameliorates the course of experimental Staphylococcus aureus arthritis

Objective. To evaluate the combined effect of systemic corticosteroid and antibiotic therapy on the course of septic arthritis. Methods. The murine model of hematogenously acquired Staphylococcus aureus arthritis was used. Mice were treated with corticosteroids and antibiotics, and were followed up individually. Arthritis was evaluated clinically and histopathologically. Serum samples and bacterial isolates were also analyzed. Results. The prevalence of arthritis 14 days after the onset of the disease was 22% in the corticosteroid and antibiotic–treated group, as compared with 81% in the control (nontreated) group and 48% in the antibiotic-treated group. The severity of arthritis also decreased in the corticosteroid and antibiotic-treated group, as did the mortality rate. Immunohistochemical analysis revealed a dramatic decrease in T cells and macrophages in the synovium of mice that took the combined therapy. The mechanisms leading to this outcome include the inhibitory effect of corticosteroids on T cell and B cell proliferation and differentiation, such as suppression of interferon-γ (IFNγ) production. Serum levels of IFNγ were decreased 4-fold in the antibiotic-treated group compared with the controls; a 15-fold decrease was observed in the corticosteroid and antibiotic–treated animals. In addition, serum NO₃⁻ was significantly decreased in mice treated with antibiotics (P ≤ 0.05), as well as in mice treated with corticosteroids and antibiotics (P ≤ 0.001). Conclusion. Systemic corticosteroid administration along with antibiotic therapy had beneficial effects on the course and outcome of S aureus arthritis.     

Interaction with Complement Receptor 1 (CD35) Leads to Amelioration of Sepsis-Triggered Mortality but Aggravation of Arthritis During Staphylococcus aureus Infection

The aim of this study was to assess the importance of complement receptor 1 (CR1, CD35) in Staphylococcus aureus arthritis and sepsis. The murine model of haematogenously acquired septic arthritis was used, injecting toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus LS-1 intravenously. CR1 was blocked using immunoglobulin G (IgG) rat antimouse CR1 monoclonal antibody (MoAb) (8C12). Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of blocking CR1 was assessed on the phagocytic activity of leucocytes and on T-cell dependent and independent inflammation. Seven days after inoculation with bacteria, 96% of CR1 MoAb-treated mice had clinical symptoms of arthritis compared with 58% of the control animals (P < 0.01). The severity of arthritis, expressed as mean arthritic index, was 2.9 +/- 0.5 and 1.4 +/- 0.5, respectively (P = 0.004). Fifteen days after bacterial inoculation, all CR1 MoAb-treated mice had severe arthritis (mean arthritic index 6.3 +/- 0.6), while only 77% of controls were affected (mean arthritic index 2.9 +/- 0.6; P = 0.002). The potential explanation of these findings is that treatment with CR1 MoAb significantly increases the polymorphonuclear cell-dependent inflammatory response as a result of enhanced vasodilatation in treated animals. We conclude that treatment with CR1 MoAb leads to amelioration of sepsis-induced mortality during S. aureus infection, possibly as a result of the increased phagocytic activity of peripheral phagocytes.