Ab initio simulations of Cu binding sites in the N-terminal region of PrP

The prion protein (PrP) binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH=7.4. Recent experiments show that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square planar coordination. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the Cu coordination mode to the binding sites of the PrP octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)+(wat), Cu(HGGG) and the 2[Cu(HGGG)] dimer are presented. While the presence of a Trp residue and a H2O molecule does not seem to affect the nature of the Cu coordination, high stability of the bond between Cu and the amide Nitrogens of deprotonated Gly's is confirmed in the case of the Cu(HGGG) system. For the more interesting 2[Cu(HGGG)] dimer a dynamically entangled arrangement of the two monomers, with intertwined N-Cu bonds, emerges. This observation is consistent with the highly packed structure seen in experiments at full Cu occupancy.Comment: 4 pages, conference proceedin

Zenithal bistable device: comparison of modeling and experiment

A comparative modeling and experimental study of the zenithal bistable liquid crystal device is presented. A dynamic Landau de Gennes theory of nematic liquid crystals is solved numerically to model the electric field induced latching of the device and the results are compared with experimental measurements and theoretical approximations. The study gives a clear insight into the latching mechanism dynamics and enables the dependence of the device latching on both material parameters and surface shape to be determined. Analytical approximation highlights a route to optimize material selection in terms of latching voltages and the numerical model, which includes an accurate surface representation, recovers the complex surface shape effects. Predictions of device performance are presented as a function of both surface anchoring strength and surface shape and grating pitch. A measurement of the homeotropic anchoring energy has been undertaken by comparing the voltage response as a function of cell gap; we find the homeotropic anchoring energies can be varied in the range 0.5 to 4 (10-44 J m-2)

The Interaction of Atovaquone with the P. carinii Cytochrome bc 1 Complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92453/1/j.1550-7408.2001.tb00505.x.pd

LIMESTONE CONTACTORS AS A CORROSION CONTROL TECHNOLOGY FOR SMALL PUBLIC WATER SYSTEMS: An Educational Module for Drinking Water Professionals

This thesis includes a review of literature of the limestone contactors technology for small water systems and discusses the process and methodology involved in developing the educational module on limestone contactors. It includes most of the narrative texts presented in the module. Both this thesis and the module are intended to be used as an educational tool by small public water system operators, owners, regulators, and engineers of limestone contactors as a corrosion control method to meet the lead and copper action level stated in the U.S. EPA’s Lead and Copper Rule. This module includes the description of the processes involved in a limestone contactor, the criteria used in the design, operational and maintenance procedure, and performance data, as well as multimedia tools such as photos and interactive process diagrams to further explain the process and components involved in a limestone contactor. Data and information presented are based on limestone contactors designed in U.S., Germany and South Africa. The module is the fourth in a series of water treatment technology educational modules created by the University of Tennessee and the University of New Hampshire and the first to be available on the web

Lansoprazole-Induced Improvement of Esophageal Submucosal Injury

The proton pumpvinhibitor, lansoprazole, is reported to have acid secretion inhibiting effect as well as anti-inflammatory effects such as inhibition of cytokine secretion from inflammatory cells. Clinically, excellent efficacy of lansoprazole is reported for not only gastric ulcer but also gastroesophageal reflux disease (GERD). Since GERD is categorized endoscopically into erosive esophagitis and non-erosive reflux disease, it is important to make accurate assessment of any improvement in the inflammatory process when using endoscopic ultrasonography (EUS) capable of visualizing the submucosal structure. We report here our experience in assessing the effect of treatment with lansoprazole on esophageal wall structure using EUS in patients with GERD. At baseline (before treatment), EUS showed abnormalities in the mucosa, submucosa and muscularis propria caused by inflammation, thickening of the entire esophageal wall and changes in the contractile properties of esophageal smooth muscles reflecting the effects of inflammation on the entire wall of the lower esophagus in reflux esophagitis regardless of whether it is erosive or endoscopically-negative. Treatment with lansoprazole resulted in normalization of esophageal wall structure and improvement of motility, suggesting that lansoprazole improves not only mucosal inflammation but also submucosal inflammation in GERD

Binding interaction between (−)-epigallocatechin-3-gallate (EGCG) of green tea and pepsin

Analysis of the binding interaction of (−)-epigallocatechin-3-gallate (EGCG) and pepsin is important for understanding the inhibition of digestive enzymes by tea polyphenols. We studied the binding of EGCG to pepsin using fluorescence spectroscopy, Fourier transform infrared spectroscopy, isothermal titration calorimetry, and protein-ligand docking. We found that EGCG could inhibit pepsin activity. According to thermodynamic parameters, a negative ΔG indicated that the interaction between EGCG and pepsin was spontaneous, and the electrostatic force accompanied by hydrophobic binding forces may play major role in the binding. Data from multi-spectroscopy and docking studies suggest that EGCG could bind pepsin with a change in the native conformation of pepsin. Our results provide further understanding of the nature of the binding interactions between catechins and digestive enzymes

Effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites in rats

O objetivo deste estudo foi avaliar os efeitos da cafeína, do polifenol do chá e da daidzeína na farmacocinética do lansoprazol e de seus metabólitos. Administraram-se, intragastricamente, aos ratos cafeína (30 mg·kg-1, uma vez ao dia), polifenol do chá(400 mg·kg-1, uma vez ao dia) ou daidzeína (13,5 mg·kg-1, uma vez ao dia), por 14 dias, seguindo-se a administração de lansoprazol (8 mg·kg-1) no 15º. dia. As concentrações plasmáticas do lansoprazol e de seus dois metabólitos primários, 5-hidroxilansoprazol e sulfona de lansoprazol, foram determinadas por cromatografia líquida de alta eficiência acoplada com espectrometria de massas (CLAE-EM/EM). O polifenol do chá elevou, significativamente, a Área Sob a Curva (ASC) do lansoprazol de 680,29 ± 285,99 para 949,76 ± 155,18 μg/L.h e reduziu a da sulfona de lansoprazol de 268,82 ± 82,37 para 177,72 ± 29,73 μg/L.h. A daidzeína aumentou a ASC do lansoprazol de 680,29 ± 285,99 para 1130,44 ± 97,6 μg/L.h e reduziu a da sulfona de lansoprazol de 268,82 ± 82,37 para 177,72 ± 29,73 μg/L.h. A farmacocinética do 5-hidroxilansoprazol permaneceu intacta na presença de polifenol do chá ou daidzeína. A cafeína não afetou a farmacocinética do lansoprazol e de seus metabólitos. Os resultados sugerem que o polifenol do chá e a daidzeína podem inibir o metabolismo in vivo do lansoprazol por supressão da CYP3A.The aim of this study was to evaluate the effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites. Rats were intragastrically administered caffeine (30 mg·kg-1, once per day), tea polyphenol (400 mg·kg-1, once per day) or daidzein (13.5 mg·kg-1, once per day) for 14 days, followed by an intragastric administration of lansoprazole (8 mg·kg-1) on the 15th day. The plasma concentrations of lansoprazole and its two primary metabolites, 5-hydroxylansoprazole and lansoprazole sulfone, were determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Tea polyphenol significantly elevated the Area Under the Curve (AUC) of lansoprazole from 680.29 ± 285.99 to 949.76 ± 155.18 μg/L.h and reduced that of lansoprazole sulfone from 268.82 ± 82.37 to 177.72 ± 29.73 μg/L.h. Daidzein increased the AUC of lansoprazole from 680.29 ± 285.99 to 1130.44 ± 97.6 μg/L.h and decreased that of lansoprazole sulfone from 268.82 ± 82.37 to 116.23 ± 40.14 μg/L.h. The pharmacokinetics of 5-hydroxylansoprazole remained intact in the presence of tea polyphenol or daidzein. Caffeine did not affect the pharmacokinetics of lansoprazole and its metabolites. The results imply that tea polyphenol and daidzein may inhibit the in vivo metabolism of lansoprazole by suppressing CYP3A

Respiratory Effects of Amifostine and DRDE-07: Probable Prophylactic Agents of Sulphur Mustard in Rats

Amifostine (S-2[3-aminopropylamino]ethyl phosphorothioate) and one of its analogues,DRDE-07 (S-2[2-aminoethylamino]ethyl phenyl sulphide) are promising prophylactic agents forsulphur mustard (SM; a blistering agent) toxicity. When given orally, DRDE-07 was more effectivethan amifostine as a prophylactic agent against SM administered percutaneously. Variouspharmacological and toxicological studies are required before the introduction of a chemical asa drug. The respiratory effects of amifostine and DRDE-07 were carried out in rats using a bodyplethysmograph fitted with a volumetric pressure transducer for sensing the respiratory flowsignals. The signals were amplified, digitised, and stored on a personal computer for furtheranalysis. After taking control recordings of respiratory signals, different doses (0.5 LD50, 1.0 LD50and 2.0 LD50) of amifostine and DRDE-07 were administered orally (LD50 amifostine = 2262 mg/kg; DRDE-07 = 1599 mg/kg), and the respiratory changes were monitored for 4 h. Amifostine andDRDE-07 showed a uniform breathing pattern even in 2.0 LD50 dose. However, a significant dosedependentdecrease in respiratory frequency was observed following amifostine administration.DRDE-07 did not show any significant change. The tidal volume was not altered significantlyboth in amifostine and DRDE-07 administered animals. The study shows that DRDE-07, even inlethal doses, may not affect the respiration immediately, whereas, amifostine may decrease therespiratory frequency