Bildgebung rheumatischer Erkrankungen

Differential diagnostics of arthritides is challenging even for experienced radiologists. Nevertheless, there are simple signs that can give important clues to make a diagnosis. Close cooperation with the attending clinicians is essential to get the most from imaging studies and to provide relevant information for patient management and therapy.     

A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium‐activated chloride secretion in human sweat gland epithelial cells

Sweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca²⁺‐activated Cl^? channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL‐SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A‐dimerization domain. Chloride flux assays using halide‐sensitive YFP revealed that TMEM16A is functionally involved in Ca²⁺‐dependent Cl^? secretion in NCL‐SG3 cells. Recombinant expression in NCL‐SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca²⁺‐activated Cl^? permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland‐specific Cl^? secretion providing opportunities to develop sweat gland‐specific therapeutics for treatment of sweating disorders.     

Comparison of different stepwise screening strategies for type 2 diabetes: Finding from Danish general practice,Addition-DK

AimTo examine attendance, number of people with T2DM and costs of three different stepwise screening strategies for T2DM in general practice (GP).MethodsDiabetes risk questionnaires were mailed to individuals aged 40–69 years from 45 general practices in 2001–2002 and individuals at high risk for T2DM, were asked to contact their GP to arrange a screening test. In 2005–2006, 26 general practices were randomised into two different opportunistic screening programmes (OP-direct and OP-subsequent) and risk questionnaires were distributed to individuals aged 40–69 years during GP consultations. In the OP-direct approach, high-risk individuals were offered to start the screening during the actual consultation while high-risk individuals in the OP-subsequent approach, were invited to a screening test at a later date. We report attendance, number of people with T2DM and costs of each screening approach.ResultsThe mail-distributed approach identified 0.8% of the target population with T2DM, the OP-direct approach and the OP-subsequent approach, 0.9% and 0.5% respectively. Cost per person with T2DM was in the mail-distributed approach: € 1058, OP-direct approach: € 707 and the OP-subsequent approach: € 727.ConclusionThis study indicates that opportunistic screening identifies the same level of unknown diabetes as a mail-distributed approach but with lower costs.     

A Cell-Free Collagen Type I Device for the Treatment of Focal Cartilage Defects

The purpose of this study was to evaluate the potential value of a cell-free collagen type I gel plug for the treatment of focal cartilage defects. Cellular migration and proliferation was addressed in vitro, and the formation of repair tissue in a nude mouse-based defect model. A cell-free plug made of collagen type I was placed in the center of an incubation plate. Surrounding space was filled with a collagen type I gel (Arthro Kinetics, Esslingen, Germany) seeded with 2 × 10⁵ human articular chondrocytes/mL gel. After cultivation for up to 6 weeks in vitro, samples were subject to histological and immunohistochemical staining and gene expression analysis. Subsequently, chondral defects of human osteochondral blocks were treated with the plug, and specimens were cultivated subcutaneously in nude mice for 6 weeks. The repair tissue was evaluated macroscopically, and collagen type II production was investigated immunohistochemically. In vitro, morphology of immigrated cells did not show any differences, as did collagen type II gene expression. After 4 weeks, the plug was homogeneously inhabited. After 6 weeks of cultivation in nude mice, collagen gel plug treatment led to a macroscopically excellent repair tissue. Histological staining revealed a tight bonding, and the collagen gel plug started to be remodeled. We conclude that the novel collagen gel plug device offers an environment favorable for the migration of articular chondrocytes and leads to a good-quality repair tissue in the nude mouse model. The arthroscopic transplantation of a collagen gel plug may be one option in the treatment of focal cartilage defects.     

Reversible interconversion of carbon dioxide and formate by an electroactive enzyme

Carbon dioxide (CO₂) is a kinetically and thermodynamically stable molecule. It is easily formed by the oxidation of organic molecules, during combustion or respiration, but is difficult to reduce. The production of reduced carbon compounds from CO₂ is an attractive proposition, because carbon-neutral energy sources could be used to generate fuel resources and sequester CO₂ from the atmosphere. However, available methods for the electrochemical reduction of CO₂ require excessive overpotentials (are energetically wasteful) and produce mixtures of products. Here, we show that a tungsten-containing formate dehydrogenase enzyme (FDH1) adsorbed to an electrode surface catalyzes the efficient electrochemical reduction of CO₂ to formate. Electrocatalysis by FDH1 is thermodynamically reversible—only small overpotentials are required, and the point of zero net catalytic current defines the reduction potential. It occurs under thoroughly mild conditions, and formate is the only product. Both as a homogeneous catalyst and on the electrode, FDH1 catalyzes CO₂ reduction with a rate more than two orders of magnitude faster than that of any known catalyst for the same reaction. Formate oxidation is more than five times faster than CO₂ reduction. Thermodynamically, formate and hydrogen are oxidized at similar potentials, so formate is a viable energy source in its own right as well as an industrially important feedstock and a stable intermediate in the conversion of CO₂ to methanol and methane. FDH1 demonstrates the feasibility of interconverting CO₂ and formate electrochemically, and it is a template for the development of robust synthetic catalysts suitable for practical applications.     

Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases

Purpose

Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.

Results

IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.

Conclusions

Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.