Regulation of endothelial permeability by beta-adrenoceptor agonists: contribution of beta 1- and beta 2-adrenoceptors

The barrier function of cultured, macrovascular endothelial cells derived from bovine aorta was analyzed using confluent monolayers of cells and measuring the exchange of fluorescein dextrans of different molecular masses. The effects of beta-adrenoceptor agonists with different selectivity for beta 1- and beta 2-adrenoceptors (AR) were investigated. Formoterol, a novel high-affinity agonist for beta 2-AR recently introduced in the treatment of bronchial asthma, showed a significant reduction of cell permeability with subnanomolar concentrations, whereas the catecholamines (-)-isoproterenol and (-)-norepinephrine only showed significant effects with micromolar concentrations. In order to elucidate if this difference in potential to regulate cell permeability is related to appropriate changes in the selectivity and affinity of the agonists for beta 2 AR, we investigated the beta AR-coupled adenylate cyclase (AC) in membranes from endothelial cells and compared AC stimulation with the binding of agonists to the receptors using [125I](-)-iodopindolol as radioligand. beta-Adrenoceptors revealed to be closely coupled to AC as assessed by a similar magnitude of effects by receptor agonists in comparison to GTP analogues and direct stimulants of AC activity. AC activity was increased by formoterol in parallel to its receptor occupancy of beta 2AR with nanomolar concentrations which were 50-fold higher than those used for the regulation of cell permeability indicating the existence of spare receptors. In contrast to formoterol, the catecholamines (-)-isoproterenol and (-)-norepinephrine stimulated AC activity through both beta 1AR and beta 2AR. From the overproportional high contribution of beta 1AR to AC stimulation (42%) in comparison to its low fraction (13%) in receptor binding we calculated that beta 1AR is 3-4-fold more effectively coupled to AC than beta 2 AR.     

Consideration of Core Segregations on the Formability of Bearing Steel

In this paper the influence of core segregations on the formability of workpieces made of bearing steel is analysed and discussed on the basis of compression tests. First the necessary material properties and flow curves, taken at different regions of the bar stock material, were investigated. The core segregation material shows significantly higher flow stress at higher strain rates than the surrounding segregation‐free material. Further a strong influence of the forming temperature on the flow stress was found. On basis of these findings an FEM‐model was developed, that considers the core segregation properties, its shape and position. The results of the compression simulation with this model show a clear impact of the inhomogeneous material properties on the stress distribution.     

Personalisierung und informationelle Selbstbestimmung Ein unauflösbarer Widerspruch?

Ohne Zusammenfassung     

Membrane bending modulus and adhesion energy of wild-type and mutant cells of Dictyostelium lacking talin or cortexillins

We have employed an interferometric technique for the local measurement of bending modulus, membrane tension, and adhesion energy of motile cells adhering to a substrate. Wild-type and mutant cells of Dictyostelium discoideum were incubated in a flow chamber. The flow-induced deformation of a cell near its adhesion area was determined by quantitative reflection interference contrast microscopy (RICM) and analyzed in terms of the elastic boundary conditions: equilibrium of tensions and bending moments at the contact line. This technique was employed to quantify changes caused by the lack of talin, a protein that couples the actin network to the plasma membrane, or by the lack of cortexillin I or II, two isoforms of the actin-bundling protein cortexillin. Cells lacking either cortexillin I or II exhibited reduced bending moduli of 95 and 160 k(B)T, respectively, as compared to 390 k(B)T, obtained for wild-type cells. No significant difference was found for the adhesion energies of wild-type and cortexillin mutant cells. In cells lacking talin, not only a strongly reduced bending modulus of 70 k(B)T, but also a low adhesion energy one-fourth of that in wild-type cells was measured.     

Ultrasonic fabrication of micro nozzles from a stack of PVDF foils for generating and characterizing microfluidic dispersions

Microsystem Technologies - Nozzles with circular cross-section and a diameter varying in axial direction have been fabricated in a microfluidic channel from polyvinylidene fluoride as chemically...     

Ultrasonic Fabrication of Polymer Plate Reactors with a Surface Coating

Microreactors offer several advantages compared to the industrial scale when developing new chemical processes. Especially the production and investment costs are low if polymer microreactors are generated by ultrasonic processes. In order to observe the chemical reaction and the flow configuration, these microreactors need to be optically transparent, mechanically stable, and chemically inert to several reagents. The manufacturing process of a transparent polymer plate reactor with a chemically inert surface coating by ultrasonic fabrication is described. Experimental characterization of the microreactors showed that they are leak tight up to a pressure difference of at least 300 kPa and the mixing times are in the range of milliseconds.     

Dormia baskets impacted in the bile duct: release by extracorporeal shock-wave lithotripsy

BACKGROUND AND STUDY AIMS: Endoscopic extraction of bile duct stones may be complicated by impaction of the Dormia basket with captured stones, or rupture of the traction wire of the basket during mechanical lithotripsy. In an attempt to release impacted baskets by nonoperative means, we studied the efficacy of extracorporeal shock-wave lithotripsy in this dangerous clinical situation. PATIENTS AND METHODS: Fourteen extracorporeal shock-wave treatments were performed in 12 consecutive patients (eight women and four men; mean age 73.2 +/- 13.2 years, range 46-86 years) with an electrohydraulic shock-wave lithotriptor, using fluoroscopy (n = 13) or ultrasound (n = 1) for targeting. A total of 1845 +/- 334 (mean +/- SD) shock-wave discharges at a voltage of 22 +/- 4 kV were delivered per treatment. Nine treatment sessions (64%) were performed while patients were under general anesthesia. An attempt to extract the Dormia basket was made after disintegration of the captured stone had been confirmed by fluoroscopy. RESULTS: It was possible to remove the Dormia basket by nonsurgical means in 11 of the 12 patients (92%) after one treatment session, and after three treatment sessions in the remaining patient. Thus, disintegration of the stones allowed extraction of the Dormia basket in all patients. None of the patients needed surgical intervention. All patients were rendered free of bile duct stones after extracorporeal shock-wave lithotripsy and subsequent endoscopic removal of the fragments. No adverse effects of shock-wave therapy with subsequent extraction of the Dormia baskets were observed. CONCLUSION: Shock-wave therapy represents a primary nonsurgical therapeutic option in patients with either impacted Dormia baskets or broken devices which cannot be extracted by endoscopic means.