A preliminary study in Wistar rats with enniatin : A contaminated feed

A 28-day repeated dose preliminary assay, using enniatin A naturally contaminated feed through microbial fermentation by a Fusarium tricinctum strain, was carried out employing two months-old female Wistar rats as in vivo experimental model. In order to simulate a physiological test of a toxic compound naturally produced by fungi, five treated animals were fed during twenty-eight days with fermented feed. As control group, five rats were fed with standard feed. At the 28th day, blood samples were collected for biochemical analysis and the gastrointestinal tract, liver and kidneys were removed from each rat for enniatin A detection and quantitation. Digesta were collected from stomach, duodenum, jejunum, ileum and colon. Enniatin A present in organs and in biological fluids was analyzed by liquid chromatography-diode array detector (LC-DAD) and confirmed by LC-mass spectrometry linear ion trap (MS-LIT); also several serum biochemical parameters and a histological analysis of the duodenal tract were performed. No adverse effects were found in any treated rat at the enniatin A concentration (20.91 mg/kg bw/day) tested during the 28-day experiment. Enniatin A quantitation in biological fluids ranged from 1.50 to 9.00 mg/kg, whereas in the gastrointestinal organs the enniatin A concentration ranged from 2.50 to 23.00 mg/kg. The high enniatin A concentration found in jejunum liquid and tissue points to them as an absorption area. Finally, two enniatin A degradation products were identified in duodenum, jejunum and colon content, probably produced by gut microflora

Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization

Experimental studies and limitations of the light trapping and optical losses in microcrystalline silicon solar cells

This Study addresses the potential of different approaches to improve the generated current in silicon thin-film solar cells and modules. Decreasing the carrier concentration in the front contact has proven to increase the quantum efficiency and the cell-current density significantly. Additionally, an optically improved ZnO/Ag back reflector and the optimized light incoupling by anti-reflection layers were studied. In this contribution, we show the potential of the different optical components and discuss combinations thereof in order to obtain a maximized cell-current density in silicon thin-film solar cells. Limitations Of the cell-current density are discussed with respect to theoretical calculations. (C) 2008 Elsevier B.V. All rights reserved

MICS-1 interacts with mitochondrial ATAD-3 and modulates lifespan in C. elegans.

Contains fulltext : 108590.pdf (publisher's version ) (Closed access)Caenorhabditis elegans open reading frame T21C9.1 encodes an uncharacterized protein, which is here named MICS-1 (mitochondrial scaffolding protein-1). It is predicted to be the homolog of human outer mitochondrial membrane protein 25 (OMP25 or synaptojanin-2-binding protein), which is a PDZ domain containing protein with a putative role in cellular stress response pathways. Here, we provide evidence that MICS-1 is an interacting partner of mitochondrial protein ATAD-3 (homologue of human ATAD3), which is essential for C. elegans development. We demonstrate that mics-1(RNAi) animals or mics-1 mutants display enhanced longevity with an increased mean lifespan of up to 54% compared to control animals. Of note, also atad-3(RNAi) promoted longevity, although to a lesser extend (29% compared to controls). In addition, thermal stress of mics-1 mutants induced low reactive oxygen species (ROS) production, whereas atad-3(RNAi) animals were highly sensitive to this assay, displaying drastically increased ROS levels. Further studies revealed that MICS-1 and ATAD-3 associated longevity was partially dependent on the presence of DAF-16. However, for both conditions, we also found a DAF-16 independent extension of lifespan. Finally, we observed an additional lifespan extension in mics-1 mutants when subjected to atad-3(RNAi) whereas heat induced ROS production was even aggravated under this condition. This suggests (partially) independent effects of MICS-1 and ATAD-3 on lifespan and ROS production in vivo.1 maart 201

Experimental studies and limitations of the light trapping and optical losses in microcrystalline silicon solar cells

This Study addresses the potential of different approaches to improve the generated current in silicon thin-film solar cells and modules. Decreasing the carrier concentration in the front contact has proven to increase the quantum efficiency and the cell-current density significantly. Additionally, an optically improved ZnO/Ag back reflector and the optimized light incoupling by anti-reflection layers were studied. In this contribution, we show the potential of the different optical components and discuss combinations thereof in order to obtain a maximized cell-current density in silicon thin-film solar cells. Limitations Of the cell-current density are discussed with respect to theoretical calculations. (C) 2008 Elsevier B.V. All rights reserved

Prenylated flavonoid derivatives from the bark of Erythrina addisoniae.

noTwo new prenylated flavanones, 2S-3¿-(2-hydroxy-3-methylbut-3-enyl)licoflavone-4¿-methyl ether (3) and 2S-3¿-(2- hydroxy-3-methylbut-3-enyl)abyssinone II (4), and four known flavanones (1, 2, 5, 6) were isolated from the stem bark of Erythrina addisoniae. The structures were elucidated on the basis of their spectroscopic and physicochemical data. None of the compounds showed antioxidative properties. 4¿-Methylabyssinone V (1) and abyssinoflavanone VII (6) showed moderate cytotoxic activity (IC50 ) 5 and 3.5 ¿mol/L, respectively), but apoptosis (caspase-3/7-activation, nuclear fragmentation) was selectively induced by abyssinoflavanone VII (6)

Gold(i) complexes of water-soluble diphos-type ligands: Synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition

Gold(I) complexes of imidazole and thiazole-based diphos type ligands were prepared and their potential as chemotherapeutics investigated. Depending on the ligands employed and the reaction conditions complexes [L(AuCl)2] and [L2Au]X (X = Cl, PF6) are obtained. The ligands used are diphosphanes with azoyl substituents R2P(CH2)2PR2 {R = 1-methylimidazol-2-yl (1), 1-methylbenzimidazol-2-yl (4), thiazol-2-yl (5) and benzthiazol-2-yl (6)} as well as the novel ligands RPhP(CH2)2PRPh {R = 1-methylimidazol-2-yl (3)} and R2P(CH2)3PR2 {R = 1-methylimidazol-2-yl (2)}. The cytotoxic activity of the complexes was assessed against three human cancer cell lines and a rat hepatoma cell line and correlated to the lipophilicity of the compounds. The tetrahedral gold complexes [(3)2Au]PF6 and [(5)2Au]PF6 with intermediate lipophilicity (logD7.4 = 0.21 and 0.25) showed significant cytotoxic activity in different cell lines. Both compounds induce apoptosis and inhibit the enzymes thioredoxin reductase and glutathione reductase