HDL3-mediated cholesterol efflux from cultured enterocytes: The role of apoproteins A-I and A-II

High density lipoproteins (HDL) were recently demonstrated in an enterocyte model (CaCo-2 cells) to mediate reverse cholesterol transport by retroendocytosis. The present study was carried out to define the role of the major HDL apoproteins (apo) A-I and apo A-II in this pathway. HDL₃ was fractionated by heparin affinity chromatography into the two main fractions containing either apo A-I only (fraction A) or both apo A-I and apo A-II (fraction B). In addition, liposomes were reconstituted from purified apo A-I or apo A-II and dimyristoyl phosphatidylcholine. The cell binding properties and cholesterol efflux potential were studied in the lipoprotein fractions and the liposomes. Both fractions exhibited similar maximal binding capacities of 4427 (A) and 5041 (B) ng/mg cell protein, but their dissociation constants differed (40.5 and 167.7 μg/mL, respectively). Fraction A induced cholesterol efflux and stimulated cholesterol synthesis more than did fraction B. Fraction A mobilized both cellular free and esterified cholesterol, whereas fraction B preferentially mobilized cholesteryl esters. Liposomes, containing either apo A-I or apo A-II, showed specific binding, endocytosis and endosomal transport, and were released as intact particles. Apo A-I liposomes also mediated cholesterol efflux. In conclusion, there is evidence that the HDL₃ subfractions A and B, as well as reconstituted liposomes containing either apo A-I or apo A-II, were specifically bound and entered a retroendocytosis pathway which was directly linked to cholesterol efflux. Quantitatively, the apo A-I subfraction appeared to play the dominant role in normal enterocytes. The apo A-II content of fraction B was related to the mobilization of cholesteryl esters.     

Beyond Heparinization: Design of Highly Potent Thrombin Inhibitors Suitable for Surface Coupling

During extracorporeal circulation, when blood comes in contact with artificial surfaces, patients receive a standard treatment with anticoagulants to avoid blood coagulation. Dialysis patients in particular are systemically treated with heparin up to four times a week, causing a high burden for the body. For potential anticoagulant modification of external materials, such as dialysis equipment, a series of highly potent thrombin inhibitors was developed. All inhibitors share the general formula arylsulfonyl‐P3‐Pro‐4‐amidinobenzylamide, where P3 is glycyl or a trifunctional amino acid residue in L ‐configuration. Among this series, several derivatives inhibit thrombin with K_i values of less than 1 nM . Specificity measurements revealed that this inhibitor type is highly specific for thrombin with negligible activity against related trypsin‐like serine proteases. X‐ray analysis of the most potent analogue in complex with thrombin demonstrated that the N‐terminal arylsulfonyl group occupies the aryl binding site, whereas the P3 side chain is directed into the solvent and therefore is well suited for further coupling. Based on their in vitro profile, these inhibitors are suitable candidates for the development of hemocompatible materials with anticoagulant properties.     

Synthesis of Ultrahigh-Temperature Si–B–C–N Ceramic from Polymeric Waste Gas

A "green" route to ultrahigh-temperature Si–B–C–N ceramic from vacuum-degassing waste gas of polyborosilazane {B[C₂H₄Si(CH₃)NH]₃} _n (T2-1) has been developed. After gas-to-gel transformation, an amorphous ceramic Si_5.3B_1.0C₁₉N_3.7 was derived from the gel by dehydrocoupling and polymer-to-ceramic transformation. The ceramic started to form a nanostructure at 1700°C and resisted thermal degradation up to 2200°C in argon. This suggests that vacuum-degassing waste gases of polymer precursors may be perfect raw materials for various advanced ceramics.     

Semi‐Markovian modelling and performance analysis of variable rate traffic in ATM networks

Semi‐Markovian processes (SMP) serve as a versatile means to model various traffic types generated by sources or superposed from links in ATM networks. An efficient discrete time analysis method is proposed for SMP/G/1 queueing systems to evaluate ATM switches with non‐renewal input. Some basic results are derived for the autocorrelation function of semi‐Markovian processes and for the effect of state space reduction on autocorrelation, which show how to represent correlated traffic with given characteristic by an adequate SMP model of limited size. This revised version was published online in June 2006 with corrections to the Cover Date.     

Muscular capabilities and workload of flight attendants for pushing and pulling trolleys aboard aircraft

Increasingly in the recent years, passengers’ services are extended into the ascent and descent flight phases on short distance flights. Trolleys containing the required meal and beverage items are used for these service operations and pushed or pulled along the aisles of the aircraft. Flight attendants reported about increased musculo-skeletal disorders and had been complaining about high physical workload from handling trolleys. In order to ensure acceptable load levels for pushing or pulling operations of trolleys, the physical capabilities of the collective “flight attendants” had been investigated by means of force measurements at maximum voluntary contraction (MVC) level and associated relevant anthropometrical and biometrical data. CEN and ISO standards as well as international and national German methods were used to derive recommended force limits for pushing/pulling operations with respect to the physical capabilities of the target group “flight attendants”. Comparing these recommended limits with the force requirements per shift under various conditions of trolley handlings (inclination of the floor, type and weight of trolley, mode of handling, frequency of operation) showed that especially for higher floor inclinations and trolley weights, flight attendants work (substantially) above recommended limits. It became also apparent that the handling of half-size trolleys is unexpectedly high demanding due to high vertical force components, caused by the unfavorable location of their center of gravity.

Relevance to industry

On short-distance flights, passengers’ services are performed by means of trolleys from the ascent to the descent flight phases. Flight attendants had been complaining about high physical workload. This study offers recommendations on maximum force limits for the handling of trolleys with respect to the muscular capacities and work situations of flight attendants on short-distance flights.     

Structure and density of deposits formed on filter fibers by inertial particle deposition and bounce

The morphology and packing density of particle deposits formed by accumulation on thin steel fibers suspended in an aerosol stream were studied by confocal microscopy. Measurements were made with electrically neutral polystyrene spheres (d_P=1.3, 2.0, 2.6 and 5.2 μm) as a function of flow velocity (v=0.7–5 m/s) and fiber diameters (d_F=8 and 30 μm). Deposition under these conditions was dominated by inertia (Stokes number St=0.3–9), interception (interception parameter R=0.04–0.35) and particle bounce, with a negligible contribution from diffusion.The experiments show a systematic transition of deposit morphologies with a newly introduced particle bounce parameter β～St/R, where St and R are based on the diameter d_F of the bare fiber. Compact, forward facing deposit structures dominate in case of significant particle bounce (i.e. for β>β?, where β* represents the critical conditions for the onset of bounce on the bare fiber). Dendritic structures with pronounced sideways branching are formed at β<β*. R is of relatively little influence as an independent parameter, probably because interception occurs mostly on preexisting deposit structures with dimensions in the order of d_P.The mean porosity ε of the deposit structures was determined on the basis of contour measurements by confocal microscopy, in combination with data on the accumulated particle volume per unit fiber length (known accurately from a previous paper by Kasper, Schollmeier, Meyer, and Hoferer (2009). Once noticeable deposits had formed, ε was found to attain stable values between 0.80 at d_P=1.3 μm and 0.55 at d_p=5.2 μm.     

SEPARATION OP NITRATE FROM SULPHATE MEDIUM,IN PARTICULAR,FROM CuSO4-SOLUTIONS Br THE USE OF ION EXCHANGERS

From sulphate-containing process solutions, such as CuSO₄-solutions, nitrate can be removed by ion exchange resulting in residual contents not higher than trace amounts (< 10 mg/1). NO₃ ^?adsorption by the ion exchanger increases with increasing total electrolyte content so that, when contacted with > 1 M CuSO₄-solution, 70 % to 80 % of the capacity of traditional ion exchange resins is utilized for adsorbing the NO₃ ^? Even higher adsorption degrees have been achieved by the use of resins type wofatit SN 35 L that are selective for nitrate or a weakly basic resin with di-n-butyl amine functional groups. The resins loaded can be regenerated with alkalies and H₂SO₄. For the latter case, a closed loading-regeneration cycle is proposed which allows the separated NO₃ to be reused as HNO₃.     

Stimulation of Bone Healing by Sustained Bone Morphogenetic Protein 2 (BMP-2) Delivery

The aim of the study was to investigate the effect of a sustained release of bone morphogenetic protein2 (BMP-2) incorporated in a polymeric implant coating on bone healing. In vitro analysis revealed a sustained, but incomplete BMP-2 release until Day 42. For the in vivo study, the rat tibia osteotomy was stabilized either with control or BMP-2 coated wires, and the healing progress was followed by micro computed tomography (μCT), biomechanical testing and histology at Days 10, 28, 42 and 84. MicroCT showed an accelerated formation of mineralized callus, as well as remodeling and an increase of mineralized/total callus volume (p = 0.021) at Day 42 in the BMP-2 group compared to the control. Histology revealed an increased callus mineralization at Days 42 and 84 (p = 0.006) with reduced cartilage at Day 84 (p = 0.004) in the BMP-2 group. Biomechanical stiffness was significantly higher in the BMP-2 group (p = 0.045) at Day 42. In summary, bone healing was enhanced after sustained BMP-2 application compared to the control. Using the same drug delivery system, but a burst release of BMP-2, a previous published study showed a similar positive effect on bone healing. Distinct differences in the healing outcome might be explained due to the different BMP release kinetics and dosages. However, further studies are necessary to adapt the optimal release profiles to physiological mechanisms.