Immunologically restricted patients exhibit a pronounced inflammation and inadequate response to hypoxia in fracture hematomas.

For patients who are known to have an impaired immune system, bone healing is often impaired. Therefore, it has been suggested that an effectively functioning immune system will have an influence on the quality of bone healing. Here, we demonstrate that cells within the fracture hematoma of immunologically restricted patients (1) exhibit a disturbed osteogenic differentiation (normal SPP1 but diminished RUNX2 expression), (2) show a strong inflammatory reaction (high IL8 and CXCR4), and (3) react on local hypoxia (high expression of HIF1A) but with inadequate target gene responses (diminished LDHA and PGK1 expression).

How should impaired morning function in rheumatoid arthritis be treated?

Patients with rheumatoid arthritis (RA) commonly experience morning symptoms of joint stiffness and pain that result in impaired function. However, current treatment options are limited. The management of impaired morning function is based primarily on non-pharmacological approaches, including simple or short exercises, application of heat or a hot shower or bath, and delaying activities until later in the day.

Impact of impaired morning function on the lives and well-being of patients with rheumatoid arthritis.

Morning joint stiffness and pain are prominent features in patients suffering from rheumatoid arthritis (RA) and contribute to impaired function. A survey was conducted across 11 European countries to assess the impact of impaired morning function on patients' quality of life. A total of 518 rheumatologists, and 750 patients aged 18-75 years with RA for ≥ 6 months and impaired morning function at least three times a week, completed the structured questionnaires.

Human early fracture hematoma is characterized by inflammation and hypoxia.

Background: An effective immune system, especially during the inflammatory phase, putatively influences the quality and likelihood of bone healing. If and how this is reflected within the initial fracture hematoma is unclear.

Questions/purposes: We therefore asked the following questions: (1) Does the local expression in fracture hematoma of genes involved in adaptation to hypoxia, migration, angiogenesis, and osteogenesis vary as compared to the peripheral blood? (2) Do these changes occur time dependently? (3) Is the gene expression during fracture hematoma formation altered by irradiation?

Methods: Cells from fracture hematoma of 20 patients and hematomas formed in 40 patients after THA (20 without and 20 with preoperative radiation) were isolated and RNA was extracted to analyze the influence of oxygen deprivation during fracture healing on mRNA expression of genes (HIF1A, LDHA, and PGK1) involved in immunoregulation (IL6, IL8, CXCR4), angiogenesis (VEGF, IL8), and osteogenesis (SPP1, RUNX2) by quantitative PCR.

Macrophage migration inhibitory factor counterregulates dexamethasone-mediated suppression of hypoxia-inducible factor-1 alpha function and differentially influences human CD4+ T cell proliferation under hypoxia.

Hypoxia, a feature of inflammation and tumors, is a potent inducer of the proinflammatory cytokine macrophage migration inhibitory factor (MIF). In transformed cells, MIF was shown to modulate and to be modulated via the oxygen-sensitive transcription factor hypoxia-inducible factor (HIF)-1. Furthermore, anti-inflammatory glucocorticoids (GCs) were described to regulate MIF action.

Current view of glucocorticoid co-therapy with DMARDs in rheumatoid arthritis.

Glucocorticoids are widely used anti-inflammatory and immunosuppressive drugs for rheumatoid arthritis (RA). The disease-modifying potential of low to medium doses of glucocorticoids has been reconfirmed in the past decade, and co-administration of DMARDs and glucocorticoids has become standard in many treatment protocols, especially those for early disease stages but also for long-standing RA. The glucocorticoid regimens used range from continuous low doses to intermittent high doses.

Methotrexate treatment in large vessel vasculitis and polymyalgia rheumatica.

In large vessel vasculitis, including giant cell arteritis and Takayasu arteritis, as well as in polymyalgia rheumatica, glucocorticoid therapy is the treatment of choice. However, there are two situations/questions for additional immunosuppressive therapies in these diseases: (i) therapy resistance to glucocorticoid mono-therapy; (ii) situations which call for sparing of glucocorticoids such as in complications of glucocorticoid therapy. This review summarises the current scientific debate on the effects of methotrexate in these diseases.

The association between rheumatoid arthritis and periodontal disease.

Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress.

Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice.

Objective: To develop recommendations on monitoring for adverse events (AEs) of low-dose glucocorticoid (GC) therapy (≤7.5 mg prednisone or equivalent daily) in clinical trials and daily practice.

Methods: Literature was searched for articles containing information on incidence and monitoring of GC-related AEs using PubMed, EMBASE and Cochrane databases.

Hypothalamus-pituitary-adrenal axis function in patients with rheumatoid arthritis treated with nighttime-release prednisone.

Objective: To investigate the effects of longterm low-dose chronotherapy with modified-release (MR) prednisone for rheumatoid arthritis (RA) on the hypothalamus-pituitary-adrenal (HPA) axis as part of the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-1) study. This consisted of a 3-month active-controlled phase and a 9-month open-label extension with MR prednisone including patients previously treated with prednisone (ClinicalTrials.gov number NCT00146640).

Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis.

The role of bacterial infections in the pathogenesis of rheumatoid arthritis (RA) has gained increasing interest. Patients with RA often exhibit periodontal disease, which is associated with pathogens like Porphyromonas gingivalis. The present study examines the direct effects of P.

Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis.

Objective: This 9-month open-label extension of the Circadian Administration of Prednisone in Rheumatoid Arthritis Study (CAPRA 1) investigated the long-term safety and efficacy of prednisone chronotherapy with a novel modified-release (MR) prednisone for up to 12 months.

Methods: Of 288 patients with rheumatoid arthritis originally randomised to MR or immediate-release (IR) prednisone, 249 continued with prednisone chronotherapy (2-10 mg/day) in the 9-month open-label extension. Duration of morning stiffness of the joints (MS), disease activity scores (DAS28), American College of Rheumatology (ACR20) responses and plasma levels of interleukin 6 (IL-6) were assessed.

Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV).

Objectives: Anti-neutrophil antibodies (ANCA)-associated vasculitides (AAV) comprise different forms of small vessel vasculitis characterised by B-cell driven autoimmune processes and endothelial cell activation. Aim of this study was to correlate markers of B- and endothelial cell activation with clinical manifestations of disease in AAV.

Methods: Consecutive serum samples of patients fulfilling the Chapel Hill Consensus Conference (CHCC) and American College of Rheumatology (ACR) criteria for AAV and healthy donors were used for the determination of ANCA, B-lymphocyte stimulator (BLyS), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) levels using enzyme-linked immunosorbent assay (ELISA).

Low-dose glucocorticoid therapy in rheumatoid arthritis: an obligatory therapy.

Glucocorticoids (GCs) are used extensively in patients with rheumatoid arthritis (RA). Recent data on the efficacy of these drugs in alleviating symptoms of inflammation, but also in retarding erosive damage, are presented. In addition, a critical review of the rather limited literature on adverse effects of chronic use of low dose GCs is given.

Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells.

Rimexolone is a lipophilic glucocorticoid drug used for local application. Only few data are available describing its effects on immune cell functions. In this study we investigated the effects of rimexolone on the proliferation of human CD4+ T-cells using dexamethasone as standard reference.

More night than day--circadian rhythms in polymyalgia rheumatica and ankylosing spondylitis.

The circadian rhythm of symptoms in patients with chronic inflammatory diseases is well known. Circadian rhythms could be used to identify targets for time-adapted antiinflammatory therapies, which are administered prior to the flare of cytokine synthesis and inflammatory activity. In recent years, the diurnal variations in rheumatoid arthritis have been described precisely for pain, stiffness, and functional disability, as well as the underlying cyclic variations in hormone levels and cytokine concentrations.

Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases.

Energy regulation (EnR) is most important for homoeostatic regulation of physiological processes. Neuroendocrine pathways are involved in EnR. We can separate factors that provide energy-rich fuels to stores [parasympathetic nervous system (PSNS), insulin, insulin-like growth factor-1, oestrogens, androgens and osteocalcin] and those that provide energy-rich substrates to consumers [sympathetic nervous system (SNS), hypothalamic-pituitary-adrenal axis, thyroid hormones, glucagon and growth hormone].

Effects of hypoxia and/or lack of glucose on cellular energy metabolism and cytokine production in stimulated human CD4+ T lymphocytes.

Oxidative phosphorylation and/or glycolysis provide energy, mainly in the form of ATP, which ensures proper functioning of immune cells such as CD4(+) T lymphocytes. However, the main substrates, namely oxygen and glucose, are known to remain for a relatively short time in the inflamed tissue and in other clinical situations where immune cells need to function properly. Therefore, we examined the effect of hypoxia and/or lack of glucose on cellular energy metabolism and on cytokine secretion in stimulated human CD4(+) T lymphocytes.

Pharmacology of glucocorticoids in rheumatoid arthritis.

Glucocorticoids (GCs) provide one of the most effective treatments for rheumatoid arthritis (RA); however, their long-term use is marred by undesired side effects. Increased understanding of the mechanisms of glucocorticoid action enables the development of novel drugs, such as SEGRAs or liposomal glucococorticoids, trying to improve their benefit/risk ratio. But also trying to optimise the use of conventional glucocorticoids is a sensible approach.

The early fracture hematoma and its potential role in fracture healing.

Research regarding the potency and potential of the fracture hematoma has begun to receive increasing attention. However, currently there is a paucity of relevant literature on the capability and composition of the fracture hematoma. This review briefly summarizes the regenerative fracture healing process and the close interplay between the skeletal and immune systems.

The selective estrogen receptor alpha agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: a phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine.

Objective: Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ERalpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity.

[Pathogenesis of parodontitis in rheumatic diseases].

Inflammatory periodontal disease (PD) is a common disease worldwide that has a primarily bacterial aetiology and is characterized by dysregulation of the host inflammatory response. The degree of inflammation varies among individuals with PD independently of the degree of bacterial infection, suggesting that alteration of the immune function may substantially contribute to its extent. Factors such as smoking, education, and body mass index (BMI) are discussed as potential risk factors for PD.

Analyses of similarities and differences in glucocorticoid therapy between rheumatoid arthritis and ankylosing spondylitis - a systematic comparison.

Glucocorticoids (GCs) have powerful and potent anti-inflammatory and immunomodulatory effects and are widely established in regard to the treatment of rheumatism and other diseases. In rheumatoid arthritis (RA), GCs are used systemically at several different dosages and/or local (intraarticular) therapy. They have been shown to exert strong short-term anti-inflammatory effects but also long-term positive effects on radiographic progression of the disease.