The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; K_i=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.     

The Determinants of Debt and (Private) Equity Financing: The Case of Young, Innovative SMEs from Germany

Financial theory creates a puzzle. Some authors argue that high-risk entrepreneurs choose debt contracts instead of equity contracts since risky but high returns are of relatively more value for a loan-financed firm. Conversely, authors who focus explicitly on start-up finance predict that entrepreneurs are the more likely to seek equity-like venture capital contracts, the more risky their projects are. Our paper is an initial step towards resolving this puzzle empirically. We present microeconometric evidence on the determinants of debt and equity financing in young and innovative SMEs. We pay special attention to the role of risk for the choice of the method of financing. Since risk is not directly observable we use different indicators for financial and project risk. It turns out that our data generally confirms the hypothesis that the probability that a young high-tech firm receives equity financing is an increasing function of the financial risk. With regard to the intrinsic project risk, our results are less conclusive, as some of our indicators of a risky project are found to have a negative effect on the likelihood to be financed by private equity.     

Developmental and light-dependent changes of the cytosolic chaperonin containing TCP-1 (CCT) subunits in maize seedlings, and the localization in coleoptiles

The cytosolic chaperonin containing TCP-1 (CCT) is known to keep fold cytoskeletal proteins and is involved in the proper organization of the cytoskeleton. These studies are based on the assumption that growth responses linked to structural rearrangement of the plant cytoskeleton include the action of CCT and the need for newly synthesized tubulin. The presence of the alpha- and epsilon-subunits of CCT was investigated in soluble fractions of protein extracts from maize mesocotyls and coleoptiles at distinct growth stages. The CCT-subunits, tubulins and actin decreased in the coleoptile in response to far-red light. In addition, independent from light treatment, the amount of CCT epsilon abundance declined with age in coleoptiles and mesocotyls between 2 and 4.5 days after sowing. In contrast to CCT epsilon, no significant light regulation of CCT alpha was found in the mesocotyl. In two day old, light-grown rapidly elongating coleoptiles part of the CCT alpha subunit and the bulk of actin and tubulin was found shifted into fractions of high molecular weight complexes when compared to slowly elongating, dark grown coleoptiles. In 4.5 day old, etiolated and elongating coleoptiles, part of both CCT-subunits and cytoskeleton proteins were found in fractions of high molecular weight. A complete disappearance of these polypeptides was observed in old far-red irradiated growth-arrested coleoptiles. CCT epsilon was found to be colocalized to microtubular structures and to the nucleus. We conclude from our data that abundance of CCT-subunits in soluble extracts is dependent on age and light treatment, but independent from the growth stage of mesocotyl and coleoptile.     

Prolonged release Matrix Pellets Prepared by Melt Pelletization I. Process Variables

A melt pelletization process was investigated in an 8 litre laboratory scale high shear mixer using a formulation with paracetamol, glyceryl monostearate 40-50, and microcrystalline wax. The effects of jacket temperature, product temperature during massing, product load, massing time and impeller speed were investigated by means of factorially designed experiments. The maximum yield of pellets in the range of 500-1400μm was found to approx. 90%. For process conditions preventing deposition of moist mass, the process was found to be reproducible. Impeller speed and massing time were found to be important process variables. Remarkably low in vitro drug release rates were observed in USP-dissolution tests.     

Characterization of platelet-activating factor synthesis in glomerular endothelial cell lines

Platelet-activating factor synthesis in two transformed lines of glomerular endothelial cells was characterized and contrasted with platelet-activating factor production in macrovascular-derived endothelial cells as well as with glomerular cells of mesenchymal origin. Platelet-activating factor synthesis was assessed in intact cells and in cell-free preparations. Glomerular endothelial cells constitutively synthesize bio-active alkyl-PAF, and this basal activity can be chronically augmented by various inflammatory and thrombotic agents. In contrast, thrombin-mediated platelet-activating factor formation in bovine pulmonary aortic endothelial cells as well as in glomerular mesangial cells is acute and transient. The potential role of anti-inflammatory prostanoids to function as negative feedback modulators of thrombin- or endothelin-mediated platelet-activating factor synthesis was also investigated, as the synthesis of platelet-activating factor is often associated with the formation of these prostanoids. Indomethacin augmented receptor-mediated platelet-activating factor synthesis while prostanoids of the E and I series reduced agonist-stimulated PAF synthesis. In summary, the unique capacity of glomerular endothelial cells to respond to inflammatory stimuli with sustained platelet-activating factor synthesis is a clear indication of this cell's pivotal role in augmenting the inflammatory response in the limited environment of the glomerulus.