Further investigations into the preparation and [4+2] cycloaddition reactions of vinyl norcaradiene derivatives

Copyright © ARKAT USA, Inc The document attached has been archived with permission from the publisher.Norcaradiene derivatives derived from the copper-catalyzed intramolecular cyclopropanation reactions of 2-(5-vinyl-1,2,3,4-tetrahydronaphthalene) diazomethyl ketones have been prepared and submitted to Diels–Alder reactions with a range of dienophiles, including methyl acrylate, methyl 2-chloroacrylate, maleic anhydride and citraconic anhydride. The cycloaddition reactions gave better yields and were more selective when the vinyl norcaradienes were based on 8-methoxynaphthyl diazoketones.Lisa A. Buttle, Jonathan C. Morris, and Lewis N. Mande

A model to assess customer alignment through customer experience concepts

Business and Information Technology Alignment (BITA) has been one of the main concerns of IT and Business executives and directors due to its importance to overall company performance, especially today in the age of digital transformation. For BITA has been developed several models which in general has focused in the implementation of alignment strategies for the internal operation of the organizations and in the measurement of this internal alignment, but, there is still a big gap in measurement models of the alignment with the external environment of the organizations. In this paper is presented the design and application of a maturity measurement model for BITA with the customers, where the customers are actors of the external environment of the companies. The proposed model involves evaluation criteria and business practices which the companies ideally do for improve the relationship with their customers.Comment: 12 pages, Preprint version, BIS 2019 International Workshops, Seville, Spain, June 26 to 28, 2019, Revised Paper

Inhibition of interleukin-1β-stimulated collagenase and stromelysin expression in human tendon fibroblasts by epigallocatechin gallate ester

The medicinal benefits of green tea (Camellia sinensis) consumption have been attributed to bioavailable polyphenols, notably epigallocatechin gallate (EGCG). We have assessed the effects of EGCG and its non-esterified counterpart EGC on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, and the stromelysin, MMP-3, in human tendon-derived fibroblasts. Interleukin (IL)-1ß increased MMP-1, -3 and -13 mRNA and output at least 30-fold. EGCG reduced this stimulation, by 20–30% at 2.5 µM and more than 80% at 25 µM, and had a smaller effect on MMP-2 mRNA expression, which was not stimulated by IL-1ß. In all experiments EGCG was at least 10-fold more potent than EGC. EGCG reduced the stimulation of p54 JNK/SAPK phosphorylation by IL-1ß but did not affect p38 MAPK phosphorylation, the degradation of I?B or the activating phosphorylation of NF?B. We conclude that EGCG reduces the IL-1-stimulated expression of both collagenase and stromelysin mRNA species, an effect which may be mediated by inhibition of the JNK/SAPK pathway. Taken together with previous reports of EGCG effects on the expression and/or activity of gelatinases and aggrecanases, our results underline the importance of extracellular matrix breakdown as a potential target for the actions of green tea polyphenols

Cysteine proteinases from papaya (Carica papaya) in the treatment of experimental Trichuris suis infection in pigs: two randomized controlled trials

Background: Cysteine proteinases (CPs) from papaya (Carica papaya) possess anthelmintic properties against human soil-transmitted helminths (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm), but there is a lack of supportive and up-to-date efficacy data. We therefore conducted two randomized controlled trials in pigs to assess the efficacy of papaya CPs against experimental infections with T. suis. Methods: First, we assessed efficacy by means of egg (ERR) and adult worm reduction rate (WRR) of a single-oral dose of 450 μmol active CPs (CP450) against low (inoculum of 300 eggs) and high (inoculum of 3,000 eggs) intensity T. suis infections and compared the efficacy with those obtained after a single-oral dose of 400 mg albendazole (ALB). In the second trial, we determined and compared the efficacy of a series of CP doses (45 [CP45], 115 [CP115], 225 [CP225], and 450 [CP450] μmol) against high intensity infections. Results: CP450 was highly efficacious against both levels of infection intensity, resulting in ERR and WRR of more than 97%. For both levels of infection intensity, CP450 was significantly more efficacious compared to ALB by means of WRR (low infection intensity: 99.0% vs. 39.0%; high infection intensity; 97.4% vs. 23.2%). When the efficacy was assessed by ERR, a significant difference was only observed for high intensity infections, CP450 being more efficacious than ALB (98.9% vs. 59.0%). For low infection intensities, there was no significant difference in ERR between CP450 (98.3%) and ALB (64.4%). The efficacy of CPs increased as a function of increasing dose. When determined by ERR, the efficacy ranged from 2.1% for CP45 to 99.2% for CP450. For WRR the results varied from -14.0% to 99.0%, respectively. Pairwise comparison revealed a significant difference in ERR and WRR only between CP45 and CP450, the latter being more efficacious. Conclusions: A single dose of 450 μmol CPs provided greater efficacy against T. suis infections in pigs than a single-oral dose of 400 mg ALB. Although these results highlight the possibility of papaya CPs for controlling human STH, further development is needed in order to obtain and validate an oral formulation for human application

Assessment of the anthelmintic effect of natural plant cysteine proteinases against the gastrointestinal nematode, Heligmosomoides polygyrus, in vitro

We examined the mechanism of action and compared the anthelmintic efficacy of cysteine proteinases from papaya, pineapple, fig, kiwi fruit and Egyptian milkweed in vitro using the rodent gastrointestinal nematode Heligmosomoides polygyrus. Within a 2 h incubation period, all the cysteine proteinases, with the exception of the kiwi fruit extract, caused marked damage to the cuticle of H. polygyrus adult male and female worms, reflected in the loss of surface cuticular layers. Efficacy was comparable for both sexes of worms, was dependent on the presence of cysteine and was completely inhibited by the cysteine proteinase inhibitor, E-64. LD50 values indicated that the purified proteinases were more efficacious than the proteinases in the crude latex, with purified ficin, papain, chymopapain, Egyptian milkweed latex extract and pineapple fruit extract, containing fruit bromelain, having the most potent effect. The mechanism of action of these plant enzymes (i.e. an attack on the protective cuticle of the worm) suggests that resistance would be slow to develop in the field. The efficacy and mode of action make plant cysteine proteinases potential candidates for a novel class of anthelmintics urgently required for the treatment of humans and domestic livestock

Reconstitution of muscle F-actin from Atlantic salmon (Salmo salar L.) with carotenoids – binding characteristics of astaxanthin and canthaxanthin.

The binding of carotenoids to the myofibrillar protein F-actin purified from the white muscle of Atlantic salmon (Salmo salar L.) was studied using in vitro reconstitution. The binding of astaxanthin and canthaxanthin was saturable, and analysis revealed the presence of a single carotenoid-binding site. The dissociation constants (Kd) for actin prepared from 2.5 Kg FW fish were 1.04 ± 0.13 μg carotenoid mg-1 actin and 0.54 ± 0.11 μgmg-1 for astaxanthin and canthaxanthin, respectively. The saturation binding level (Bmax) for astaxanthin was 1.39 ± 0.07 μgmg-1 and 1.04 ± 0.08 μgmg-1 for canthaxanthin. These values were higher for F-actin prepared from organic and small (~0.5 Kg FW) salmon than for non-organic and larger, mature fish. The structural specificity of carotenoid binding revealed a preference for carotenoids that possess a keto group at C-4 on the end-group of the molecule, but the presence of hydroxyl groups at C-3 or C-4 reduced overall binding efficiency. The study suggests that the ability of myofibrillar proteins to bind carotenoids is not a limiting factor governing the deposition of carotenoids in the muscle of salmonids

A preliminary assessment of water partitioning and ecohydrological coupling in northern headwaters using stable isotopes and conceptual runoff models

Funded by European Research Council ERC. Grant Number: GA 335910 VEWA Swedish Science Foundation (SITES) Future Forest Formas (ForWater) SKB the Kempe foundation Environment Canada the Garfield Weston Foundation the Natural Sciences and Engineering Research Council of Canada (NSERC) the Northwest Territories Cumulative Impacts Monitoring ProgramPeer reviewedPublisher PD

In vitro anthelmintic effects of cysteine proteinases from plants against intestinal helminths of rodents

Infections with gastrointestinal (GI) nematodes are amongst the most prevalent worldwide, especially in tropical climates. Control of these infections is primarily through treatment with anthelmintic drugs, but the rapid development of resistance to all the currently available classes of anthelmintic means that alternative treatments are urgently required. Cysteine proteinases from plants such as papaya, pineapple and fig are known to be substantially effective against three rodent GI nematodes, Heligmosomoides polygyrus, Trichuris muris and Protospirura muricola, both in vitro and in vivo. Here, based on in vitro motility assays and scanning electron microscopy, we extend these earlier reports, demonstrating the potency of this anthelmintic effect of plant cysteine proteinases against two GI helminths from different taxonomic groups – the canine hookworm, Ancylostoma ceylanicum, and the rodent cestode, Rodentolepis microstoma. In the case of hookworms, a mechanism of action targeting the surface layers of the cuticle indistinguishable from that reported earlier appears to be involved, and in the case of cestodes, the surface of the tegumental layers was also the principal location of damage. Hence, plant cysteine proteinases have a broad spectrum of activity against intestinal helminths (both nematodes and cestodes), a quality that reinforces their suitability for development as a muchneeded novel treatment against GI helminths of humans and livestock