Abatacept in difficult-to-treat juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Gene changes in the immune system can predispose to JIA and regulation of the immune system is crucial in the pathogenesis. The goal of therapy is complete disease control using disease-modifying antirheumatic drugs (DMARDS). Activated T-cells may play a role in the immunopathology of JIA. Therefore, targeting T-cell activation is a rational approach for the treatment of JIA. Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA. Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations. Anti-ABA antibodies were more frequent when ABA concentrations were below therapeutic levels. Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade

Interaction of periodontitis and orthodontic tooth movement-an in vitro and in vivo study.

OBJECTIVES The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2). MATERIALS AND METHODS The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA. RESULTS Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro. CONCLUSIONS Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process. CLINICAL RELEVANCE Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again

Simulation of Fluid Flow During Direct Synthesis of H2_{2}O2_{2} in a Microstructured Membrane Reactor

A microstructured membrane reactor has been developed to overcome the safety and productivity challenge of the direct synthesis of hydrogen peroxide. A single membrane is employed for separate, continuous dosage of the gaseous reactants hydrogen and oxygen to the solid catalyst present in the aqueous solvent. Using a custom OpenFOAM® model, the impact of catalyst‐coated static mixers with different mixer geometries is studied. It is demonstrated that the custom fluid guiding elements outperform the investigated commercial static mixer under the flow conditions relevant to this application

Transition to siblinghood causes a substantial and long-lasting increase in urinary cortisol levels in wild bonobos

In animals with slow ontogeny and long-term maternal investment, immatures are likely to experience the birth of a younger sibling before reaching maturity. In these species, the birth of a sibling marks a major event in an offspring's early life, as the older siblings experience a decrease in maternal support. The transition to siblinghood (TTS) is often considered to be stressful for the older offspring, but physiological evidence is lacking. To explore the TTS in wild bonobos, we investigated physiological changes in urinary cortisol (stress response), neopterin (cell-mediated immunity), and total triiodothyronine (T3, metabolic rate), as well as changes in behaviors that reflect the mother-offspring relationship. Following a sibling's birth, urinary cortisol levels of the older offspring increased fivefold, independent of their age, and remained elevated for seven months. The cortisol level increase was associated with declining neopterin levels, however T3 levels and behavioral measures did not change. Our results indicate that the TTS is accompanied by elevated cortisol levels and that this change does not coincide with nutritional weaning and attainment of physical independence. Our results suggest that bonobos and humans experience TTS in similar ways and that this developmental event may have emerged in the last common ancestor

Apelin Enhances the Effects of Fusobacterium nucleatum on Periodontal Ligament Cells In Vitro.

This study aimed to explore effects of Fusobacterium nucleatum with or without apelin on periodontal ligament (PDL) cells to better understand pathomechanistic links between periodontitis and obesity. First, the actions of F. nucleatum on COX2, CCL2, and MMP1 expressions were assessed. Subsequently, PDL cells were incubated with F. nucleatum in the presence and absence of apelin to study the modulatory effects of this adipokine on molecules related to inflammation and hard and soft tissue turnover. Regulation of apelin and its receptor (APJ) by F. nucleatum was also studied. F. nucleatum resulted in elevated COX2, CCL2, and MMP1 expressions in a dose- and time-dependent manner. Combination of F. nucleatum and apelin led to the highest (p < 0.05) expression levels of COX2, CCL2, CXCL8, TNF-α, and MMP1 at 48 h. The effects of F. nucleatum and/or apelin on CCL2 and MMP1 were MEK1/2- and partially NF-κB-dependent. The combined effects of F. nucleatum and apelin on CCL2 and MMP1 were also observed at protein level. Moreover, F. nucleatum downregulated (p < 0.05) the apelin and APJ expressions. In conclusion, obesity could contribute to periodontitis through apelin. The local production of apelin/APJ in PDL cells also suggests a role of these molecules in the pathogenesis of periodontitis

MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes

To assess the sensitivity of the phagocyte-specific molecules myeloid-related protein (MRP) 8 and MRP14 (calprotectin) for monitoring disease activity during anti-interleukin (IL)-1 therapies in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular (CINCA) syndrome