ATP-dependent K(+) channels are composed of pore-forming subunits of the Kir6.x family and of sulfonylurea receptors (SURs). SUR1, expressed in pancreatic beta-cells, has a higher affinity for sulfonylureas, such as glibenclamide, than SUR2B, expressed in smooth muscle. This difference is mainly caused by serine 1237 in SUR1 corresponding to tyrosine 1206 in SUR2B. To increase the affinity of SUR2B for glibenclamide, the mutant SUR2B(Y1206S) was constructed. In whole-cell patch-clamp experiments, glibenclamide inhibited the channel formed by coexpression of mutant SUR2B with Kir6.1 or 6.2 in human embryonic kidney cells with IC(50) values of 2.7 and 13 nM, respectively (wild-type, 43 and 167 nM). In intact cells, [(3)H]glibenclamide bound to mutant SUR2B with a K(D) value of 4.7 nM (wild-type, 32 nM); coexpression with Kir6.1 or 6.2 increased affinity by 4- and 8-fold, respectively. Binding of the opener [(3)H]P1075 to SUR2B(Y1206S) was the same as to wild-type and was unaffected by coexpression. In cells, the ratio of glibenclamide:P1075 sites was approximately 1:1; in membranes, it varied with the MgATP concentration. Heterologous competition curves were generally biphasic; the shape of the curve depended on the Kir-subtype. The effects of coexpression were weakened or abolished when binding assays were conducted in membranes. It is concluded that the mutation Y1206S increases the affinity of SUR2B for and the channel sensitivity toward glibenclamide by 7- to 15-fold. The interaction of glibenclamide (but not opener) with mutant SUR2B is modified by coexpression with Kir6.x in a manner depending on the Kir subtype and on the integrity of the cell.

Frankfurt a. M.]Phenology and seasonality of the population response patterns of marine zooplankton provide a measure of the impact of climatic forcing upon the ecosystem, as most metazoans in the sea are periodically planktonic, usually in their pr0pagative phase. The global warming expectancy suggests intensified consideration of this aspect of ecosystem research. On the basis of the "Helgoland Roads zooplankton" time-series, such population specific investigations have been carried out. They suggest that temperature and wind stress modify the beginning, end, length and intensity of the seasonality of zooplankton populations. Climatic forcing and solar irradiation forcing of the production driven trophic cycles are basically independent of each other. The response patterns vary, depending on the life-cycle strategy of each population. Positive and negative correlation with water temperature occur, as well as larger of smaller deviations from multi-annual means, and distances from the times of greatest temperature impact and population responses. Examples are given for the different kinds of response. The results are discussed with respect to the influx of the NAO and to the annual recruitment of marine metazoans.

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Adipokines are adipose tissue-derived factors not only playing an important role in metabolism but also influencing other central processes of the body, such as inflammation. In autoimmune diseases, adipokines are involved in inflammatory pathways affecting different cell types. Many rheumatic diseases belong to the group of autoimmune diseases, for example rheumatoid arthritis (RA) and psoriatic arthritis. Due to the autoimmune responses, a chronic inflammatory milieu develops, which affects the whole body, including adipose tissue. Metabolic alterations such as obesity influence inflammatory responses in autoimmune diseases. Adipokines are bioactive mediators mainly produced by adipose tissue. Due to alterations of systemic adipokine levels, their role as biomarkers with diagnostic potential has been suggested in the context of rheumatic diseases. In the affected joints of RA patients, different synoviocytes but also osteoclasts, osteoblasts, and chondrocytes produce several adipokines, contributing to the unique inflammatory microenvironment. Adipokines have been shown to be potent modulatory effectors on different cell types of the immune system but also local cells in synovial tissue, cartilage, and bone. This review highlights the most recent findings on the role of adipokines in the pathophysiology of inflammatory arthritis with a distinct focus on RA in the quickly developing research field.

Dercum's disease which is also termed lipomatosis dolorosa is a rare and relatively unknown disease. In this entity the upper arms, elbows, stomach wall, buttocks, thighs and knees are predominantly affected showing painful subcutaneous adipose tissue deposits. In addition severe hyperalgesia can be triggered by light pressure and touch. Analgesic and/or nonsteroidal antirheumatic drugs have usually only a minor or no effect. Here, we report a patient with Dercum's disease who was successfully treated with pregabalin and manual lymphatic drainage, and present a current overview of the literature.

Profilins purified from Zea mays transiently enhance the viscosity of polymerizing cardiac actin at ratios (profilin: actin) < 1, but lower the viscosity at higher ratios. Specific binding of actin from the alga Chara corallina to higher plant profilins suggests strict conservation of interaction between both proteins in plants.

Background. Previous research on the combined association of 25-hydroxyvitamin D [25(OH)D] and exocrine pancreas insufficiency may have been limited by restricted age variability and a lack of representation of both body weight and body mass index. There are still too few conclusive reports about conspicuous vitamin D metabolism according to pancreatic fecal elastase 1 (FE1) in obese patients. Methods. Between May 2004 and July 2008, we investigated in 125 female patients with obesity syndrome at an average age of approximately 52.9 years as well as in age-matched 80 healthy female controls the prevalence of pancreas insufficiency. Serum levels of PTH, total calcium, and D3 vitamins calcitriol and calcifediol, as well as the concentration of fecal elastase 1 (FE1) were determined in patients and controls. Results. In 75 female nondiabetic patients with obesity syndrome (BMI 35 ≤ 40 kg/m2), calcifediol was markedly decreased (25.0 ± 4.9 ng/mL) compared to controls (50.2 ± 14.7 nmol/L; P < 0.01). FE1 level was significantly decreased in obese subjects compared to controls ( P < 0.01). Calcifediol was significantly lower in patients with morbid obesity (for calcifediol,  P < 0.05). Conclusion. In obese females, pancreatic FE1 in feces confirms the extent of vitamin D supply, and thus shows a vitamin D3 deficiency, depending on the loss of stool content. There seems to be a connection between the loss of exocrine function and the increasing body mass index. Pancreas insufficiency, as detected by low FE1 concentrations, is frequent in obese patients. However, the BMI is an additional factor for lowered fecal excretion of FE1.

Water temperature exhibits a strong influence on the regional variability in activity of the 7-ethoxyresorufin-O-deethylase (EROD) in the liver of dab (Limanda limanda) from the German Bight during the spawning and postspawning seasons. The relationship between EROD activity and water temperature found in situ was, surprisingly, not masked by migrations of dab. Correlations between EROD activity and temperature could not be explained by a direct temperature effect in terms of temperature compensation. Instead, we suppose that temperature influences EROD activity indirectly via its influence on the duration of the gonadal cycle and thus on the time of spawning, which we assume to be coupled with the seasonal variation in EROD activity. Significant negative correlations between EROD activity and the condition factor, gonadosomatic index, and liver-length index could be attributed to the parallel or opposite temporal changes of these parameters. In the liver of spawning females, no linear relationship was detected between the EROD activity and the concentration of the polychlorinated biphenyls (PCB), which have been previously determined.