Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells

1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na⁺/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.     

Synthesis of amphiphilic magnetic microspheres by dispersion copolymerization of styrene and poly(ethylene oxide) macromonomer

Amphiphilic magnetic microspheres ranging in diameter from 5 to 100 µm were prepared by dispersion copolymerization of styrene and poly(ethylene oxide) vinylbenzyl (PEO‐VB) macromonomer (MPEO) in the presence of Fe₃O₄ magnetic fluid. The effects of various polymerization parameters on the average particle size were systematically investigated. The average particle size was found to increase with increasing styrene concentration and initiator concentration. It also increased with decreasing stabilizer concentration and molecular weight of MPEO. The content of the hydroxyl groups localized in the microspheres ranged from 0.01 to 0.2 mmol g^?1. © 2003 Society of Chemical Industry     

Peer drug associations and emotional restraint: Causes or consequences of adolescents' drug use?

A 3-wave longitudinal design was used to examine the relationships among emotional restraint, peer drug associations, and gateway drug use in a sample of 1,256 middle school students. Structural equation modeling was used to compare 3 models: (1) One model viewed drug use as a consequence of emotional restraint and peer variables; (2) 1 viewed drug use as a cause of restraint and peer variables; and (3) 1 included reciprocal effects. All 3 models fit the data fairly well. However, the reciprocal model fit the data significantly better than either of the others. Within this model, low emotional restraint was significantly related to subsequent increases in gateway drug use among boys. In contrast, peer drug models and peer pressure were not related to subsequent changes in gateway drug use. Changes in peer drug models were, however, predicted by previous levels of gateway drug use. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The usefulness of the timeliness of endoscopic sphincterotomy in severe acute pancreatitis of biliary origin

There are evidence indicating that endoscopic retrograde cholangiopancreatography with sphincterotomy (ERCP+S) reduces the rate of complications in patients with severe acute biliary pancreatitis (ABP). The aim of this study was to analyze our experience in the treatment of severe ABP with ERCP+S and compare the evolution of the patients treated early (3 days or less following admission) with those treated late (after the 3rd day). A retrospective review of the clinical histories of the 16 patients with severe ABP treated with ERCP+S over the last two years is presented, analyzing their clinical features on admission and evolution. Biliary stones or biliary sludge was observed in 11 cases (69%). Nine patients had undergone early, and 7 late, ERCP+S. The patients of the latter group presented a greater number of complications during evolution than the former group (43% vs 0%; p = 0.025). The mortality of the patients of the late ERCP+S was also greater although without statistical significance (28.6% vs 0%; p = 0.15). No complication secondary to ERCP+S was detected. These findings confirm the fact that ERCP+S performed early in severe ABP significantly reduces the number of complications and is associated with a lower mortality.     

Stress analysis of spontaneous Sn whisker growth

Spontaneous Sn whisker growth is a surface relief phenomenon of creep, driven by a compressive stress gradient. No externally applied stress is required for the growth, and the compressive stress is generated within, from the chemical reaction between Sn and Cu to form the intermetallic compound Cu₆Sn₅ at room temperature. To obtain the compressive stress gradient, a break of the protective oxide on the Sn surface is required because the free surface of the break is stress-free. Thus, spontaneous Sn whisker growth is unique that stress relaxation accompanies stress generation. One of the whisker challenging issues in understanding and in finding effective methods to prevent spontaneous Sn whisker growth is to develop accelerated tests of whisker growth. Use of electromigration on short Sn stripes can facilitate this. The stress distribution around the vicinity and the root of a whisker can be obtained by using the micro-beam X-ray diffraction utilizing synchrotron radiation. A discussion of how to prevent spontaneous Sn whisker growth by blocking both stress generation and stress relaxation is given.     

The isolation of sucrose from tung kernels

Summary A non-reducing disaccharide has been isolated from the kernels of tung (Aleurites fordi Hemsl.) and identified as sucrose.     

Reduced modified quadratures for quadratic membrane finite elements

Reduced integration is frequently used in evaluating the element stiffness matrix of quadratically interpolated finite elements. Typical examples are the serendipity (Q8) and Lagrangian (Q9) membrane finite elements, for which a reduced 2 × 2 Gauss–Legendre integration rule is frequently used, as opposed to full 3 × 3 Gauss–Legendre integration. This ‘softens’ these element, thereby increasing accuracy, albeit at the introduction of spurious zero energy modes on the element level. This is in general not considered problematic for the ‘hourglass’ mode common to Q8 and Q9 elements, since this spurious mode is non‐communicable. The remaining two zero energy modes occurring in the Q9 element are indeed communicable. However, in topology optimization for instance, conditions may arise where the non‐communicable spurious mode associated with the elements becomes activated. To effectively suppress these modes altogether in elements employing quadratic interpolation fields, two modified quadratures are employed herein. For the Q8 and Q9 membrane elements, the respective rules are a five and an eight point rule. As compared to fully integrated elements, the new rules enhance element accuracy due to the introduction of soft, higher‐order deformation modes. A number of standard test problems reveal that element accuracy remains comparable to that of the under‐integrated counterparts. Copyright © 2004 John Wiley & Sons, Ltd.