Stochastic resonance in a proton pumping Complex I of mitochondria membranes.

We make use of the physical mechanism of proton pumping in the so-called Complex I within mitochondria membranes. Our model is based on sequential charge transfer assisted by conformational changes which facilitate the indirect electron-proton coupling. The equations of motion for the proton operators are derived and solved numerically in combination with the phenomenological Langevin equation describing the periodic conformational changes. We show that with an appropriate set of parameters, protons can be transferred against an applied voltage. In addition, we demonstrate that only the joint action of the periodic energy modulation and thermal noise leads to efficient uphill proton transfer, being a manifestation of stochastic resonance.

Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial.

BACKGROUND: The efficacy of oral prednisolone in patients with active ankylosing spondylitis (AS) has not been studied to date. METHODS: In this double-blind, randomised, placebo-controlled trial, patients with AS with active disease despite taking non-steroidal antirheumatic drugs were randomised to three groups in which they were either treated with 20 mg (n=13) or 50 mg (n=12) of prednisolone, or placebo (n=14), administered orally every day for a total of 2 weeks. The primary endpoint was defined as a 50% improvement of the Bath AS Disease Activity Index (BASDAI) at week 2. RESULTS: The primary endpoint was reached in 33% and 27% of the patients treated with 50 and 20 mg of prednisolone, respectively, versus only 8% on placebo (p=0.16 and p=0.30). However, the mean improvement of BASDAI score was significantly higher in the 50 mg prednisolone compared to the placebo group (2.39±0.5 vs 0.66±0.49, p=0.03), while there was only a small change in the 20 mg group (1.19±0.53; p=0.41). The results for other outcome parameters were similar. CONCLUSIONS: Oral prednisolone 50 mg per day, but not low dose prednisolone, showed a short-term response that was significantly higher than placebo. The clinical significance and the duration of this effect warrant further study.

[Practical problems by implementation of vaccination recommendations]. / Praktische Probleme bei der Umsetzung von Impfempfehlungen.

Patients with inflammatory rheumatic diseases are known to have an increased risk of infections due to the rheumatic disease itself and due to therapy with immunosuppressive agents. The most important procedure to prevent infections is vaccinations, which are usually well-tolerated. The German National Commission for Immunization ( STIKO) has published recommendations for patients with an immunodeficiency. The German Society of Rheumatology (DGRh) has generally implemented these recommendations for patients with chronic inflammatory rheumatic diseases. The immunization status of patients with rheumatic diseases is of increasing importance in routine patient care because some of the recently approved drugs may influence the strength of the immune response to vaccination. However, there is almost no information about the current immunization status and the willingness of patients with rheumatic diseases to undergo vaccination procedures in Germany. There are also no epidemiologic data on the implementation of recommendations for immunization at the level of general practitioners. Here we present the results of a prospective study on the efficacy of standardized recommendations for immunization given to different patient groups with rheumatic diseases treated in a hospital specialized in rheumatology.

Glucocorticoid treatment in spondyloarthritis.

Spondyloarthritides (SpA) are chronic inflammatory rheumatic diseases that usually affect the axial skeleton and may involve entheses and peripheral joints. The main subtypes are ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Other subtypes are reactive arthritis, arthritis associated with chronic inflammatory bowel diseases and undifferentiated axial and peripheral spondyloarthritis. Although SpA were regarded as variants of rheumatoid arthritis (RA) until the 1970s, it is now well established that the pathogenesis of SpA is quite different from that of RA. There is a lack of good clinical studies on glucocorticoid therapy in the SpA. While there is no reasonable doubt that intraarticular local therapies in SpA are as effective as in RA and other forms of arthritis, the evidence for a systemic use is at best marginal. While very high doses may be effective in some patients with AS, the possible value of low-dose corticosteroid therapy in patients with PsA has never been well addressed, with respect to either clinical efficacy or inhibition of radiographic progression. Future studies are needed to clarify this important issue for usual patient care.

Use of methotrexate in inflammatory myopathies.

The inflammatory myopathies are a heterogeneous group of diseases including dermatomyositis, polymyositis, and inclusion body myositis. Few clinical trials have been reported in myositis, it is difficult to make definitive recommendations for the treatment of these potentially life threatening diseases. In addition to treatment with corticosteroids, immunosuppressive agents and immunomodulatory therapy are used to improve disease control and reduce the long-term side effects of corticosteroids. While these treatments are commonly used in routine clinical practice, the optimal therapeutic regimen remains unclear. However, most patients with dermatomyositis or polymyositis are treated with oral high-dose prednisone combined with azathioprine or methotrexate to facilitate tapering of prednisone.

Clinical measures in rheumatoid arthritis and ankylosing spondylitis.

Except for morning stiffness, the clinical symptoms and the history of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) usually differ: the location in RA is mostly the hands and feet, and in AS rather the back. Patients with RA tend to be older (>50 years) and female, while in AS there are somewhat more often male and younger (<30 years) at onset of inflammatory back pain, the leading clinical symptom. The clinical examination of patients in the early phase of the disease is usually easier in RA, although arthralgia and arthritis may be difficult to differentiate. Joint counts are useful in states of high disease activity with polyarticular flares and more established disease. In comparison, in AS, young patients with back pain frequently show normal physical examens, a reduction of lateral spinal flexion and chest expansion are often the earliest signs which are also sensitive to change on therapy with biologics. The cervical spine may be affected in RA and AS - more frequently in advanced disease stages but rather early cases have been reported.

Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis.

OBJECTIVE: Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an important differential diagnosis in patients presenting with the clinical picture of an undifferentiated oligoarthritis (UOA). This study was undertaken to evaluate the best diagnostic approach. PATIENTS AND METHODS: 52 patients with ReA, defined by arthritis and a symptomatic preceding infection of the gut or the urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis without a preceding symptomatic infection and after exclusion of other diagnoses (UOA), were studied. The following diagnostic tests were applied for the identification of the triggering bacterium: for yersinia induced ReA-stool culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection of antibodies to yersinia; for salmonella or campylobacter induced ReA-stool culture, EIA for the detection of antibodies to salmonella and Campylobacter jejuni; for infections with shigella-stool culture; for infections with Chlamydia trachomatis-culture of the urogenital tract, microimmunofluorescence and immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis. RESULTS: A causative pathogen was identified in 29/52 (56%) of all patients with ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia trachomatis was the causative pathogen in 12/19 (63%) of the patients with urogenic ReA. In patients with the clinical picture of UOA a specific triggering bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%), salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%). CONCLUSIONS: Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.

No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Longitudinal investigation of bacterium-specific synovial lymphocyte proliferation in reactive arthritis and lyme arthritis.

BACKGROUND: Antigen-specific lymphocyte proliferation of synovial fluid mononuclear cells (SF MNC) has been reported repeatedly in reactive arthritis and Lyme arthritis; however, less information is available on serial investigations of SF MNC in the same patients. METHODS: In this study, the synovial lymphocyte proliferation to Yersinia, Chlamydia, Shigella and Borrelia burgdorferi was investigated sequentially at different time points in 28 patients with reactive arthritis, undifferentiated oligoarthritis or Lyme arthritis responding to one of these bacteria. RESULTS: The same bacterium was always recognized in arthritis triggered by Chlamydia, Shigella or Borrelia, with much variation in the proliferative response. Only the Yersinia-specific responses changed specificity, suggesting that the proliferative response to Yersinia is non-specific in some patients. CONCLUSIONS: Our data support the concept of a local antigen-specific T-cell response in reactive arthritis or Lyme arthritis but not the concept suggested by others that a switch to an autoimmune response takes place in long-standing disease.

Bacteria-specific lymphocyte proliferation in peripheral blood in reactive arthritis and related diseases.

The cellular immune response seems to be important for the pathogenesis of reactive arthritis (ReA) and a bacteria-specific lymphocyte proliferation (LP) is often found in synovial fluid (SF) of ReA patients. However, the role of the bacteria-specific LP in peripheral blood (PB) is less well defined. In this study, we investigated 215 paired samples of SF and PB from patients with ReA (n = 65), undifferentiated oligoarthritis (n = 133) and undifferentiated spondylarthropathy (n = 17) to analyse the LP in PB and SF in relation to time. In 24 out of 87 patients (27.6%) with a bacteria-specific LP in synovial fluid, a positive LP to the same bacterium was also found in PB. While a positive LP in SF was found most frequently in the first week of the arthritis, a positive LP in PB was detected in 45% of patients when investigated between weeks 2 and 4 after the onset of arthritis, but was rarely found very early and late in the course of the arthritis. The time point seems to be crucial for the investigation of an LP in PB in patients with ReA.