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Reducing the amount of municipal solid waste (MSW) fed to incineration while enhancing source separation and biological treatments is being considered a mean to protect the environment and human health and promote recycling. However, such a strategy can compromises the landfill reduction targets while the associated environmental benefits remain so far unexplored and, in any case, any potential benefit should be evaluated for specific situations. In this study we applied material flow analysis (MFA) and life cycle assessment (LCA) to quantitatively evaluate the potential impact of phasing-out incineration in Madrid, Spain. The current MSW management system was assessed against future scenarios that describe the elimination of incineration as well as the increase of source separation, recycling, composting, and anaerobic digestion. The results revealed that incineration phase-out jeopardizes landfill reduction. However, phasing-out incineration can reduce the impact on acidification, terrestrial and marine eutrophication, photochemical ozone formation, human toxicity cancer effects, and ecotoxicity. The climate impact ranges from irrelevant to largely beneficial depending on how the biogenic carbon is considered. The transition towards a renewable electricity mix and the increase in source separation of biodegradable waste seriously compromise the climate benefits of incineration over landfilling. Overall, actions are required in order to align incineration phase-out with the landfill reduction objective, namely upgrading material recovery facilities to reduce rejects and seeking alternative pathways for the rejects that will always exist., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Volatile fatty acids (VFAs) are platform molecules with numerous applications. They can be obtained by adjusting the operational conditions of anaerobic digestion to avoid methanogenesis while focusing on fermentative stages. There are gaps in the knowledge of how, from a life-cycle perspective, the fermentative process performs in VFAs production from waste, including environmental consequences of substituting common commodities in the current market. Mass and energy balances of VFAs production from protein-rich microalgal and carbohydrate-rich agro-industrial wastes were used herein as a key source of inventory data for life cycle assessment. Two waste treatment options were considered: (i) VFAs production (anaerobic fermentation) plus anaerobic digestion of the resulting waste after VFAs separation, and (ii) anaerobic digestion of the original waste for bioenergy. Several scenarios were formulated to evaluate their life-cycle performance. VFAs production generally shows a better environmental behaviour than conventional anaerobic digestion, principally due to the substitution of conventional chemicals., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

It has previously been reported that a prototypical compound (AGN 211377), which blocks pro-inflammatory prostanoid receptors (DP 1 , DP 2 , EP 1 , EP 4, FP, TP) and leaves open IP and EP 2 receptors so that their anti-inflammatory properties could be exerted, produced superior inhibitory effects on cytokine release from human macrophages compared to cyclooxygenase (COX) inhibitors. This favorable activity profile translated into animal studies, with AGN 211377 exceeding the level of inhibition afforded by COX inhibition. AGN 211377 was not, however, a practical drug candidate, having poor bioavailability and cost of goods concerns. Compound 1 (designated AGN 225660) represents a second-generation compound with an entirely different "druggable" core structure. Such a dramatic change in chemical scaffold created uncertainty with respect to matching the effects of AGN 211377. AGN 225660 inhibited RANTES, IL-8, and MCP-1 secretion by at least 50%, from TNFα activated human macrophages. Although AGN 225660 reduced TNFα-evoked MCP-1 release from human monocyte-derived macrophages, it increased LPS-induced MCP-1 secretion (up to 2-fold) from human monocyte-derived dendritic cells. However, AGN 225660 inhibited the release of IL12p 70 and IL-23 from human monocyte-derived dendritic cells stimulated by LPS by more than 70%. This effect of AGN 225660 was reproduced in part by the prototype compound AGN 211377 and a combination of selective DP 1 , EP 1 , EP 4 , FP, and TP antagonists. These findings suggest important effects on T cell skewing and disease modification by this class of therapeutic agents. AGN 225660 exhibited good ocular bioavailability and was active in reducing ocular inflammation associated with phacoemulsification surgery, LPS, and arachidonic acid induced uveitis., Competing Interests: The authors declare the following competing financial interest(s): N. J. Poloso remains an Allergan Inc. employee., (© 2020 American Chemical Society.)

Hydrogen is a key product for the decarbonisation of the energy sector. Nevertheless, because of the high number of technical options available for hydrogen production, their suitability needs to be thoroughly evaluated from a life-cycle perspective. The standardised concept of eco-efficiency is suitable for this purpose since it relates, with a life-cycle perspective, the environmental performance of a product system to its value. Hence, this work benchmarks the eco-efficiency performance of renewable hydrogen produced through biomass gasification against conventional hydrogen from the steam reforming of natural gas. For the eco-efficiency assessment, the harmonised environmental indicators of global warming, acidification and cumulative non-renewable energy demand were individually used, while the product system value was based on the levelised cost of hydrogen with/without internalisation of the external socio-environmental costs associated with climate change and human health. On the one hand, when the environmental and economic performances are separately considered, hydrogen from biomass gasification performs significantly better than hydrogen from steam methane reforming under environmental aspects (e.g., greenhouse gas emissions saving of 98%), whereas the opposite conclusion was found from an economic standpoint (levelised cost of 3.59 € and 2.17 € per kilogramme of renewable and fossil hydrogen, respectively). On the other hand, when combining life-cycle environmental and economic indicators under the umbrella of the eco-efficiency assessment, it is concluded that the renewable hydrogen option outperforms the conventional one, which is further remarked when implementing socio-environmental externalities. In this regard, a relative eco-efficiency score above 14 was estimated for the renewable hydrogen option when benchmarked against conventional hydrogen., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D 2 (DP) 1 , DP 2 , prostaglandin E 2 (EP) 1 , EP 4 , prostaglandin F 2α , and thromboxane A 2 receptors but not anti-inflammatory EP 2 , prostaglandin I 2 , or EP 3 receptors. Established rodent models of ocular inflammatory diseases were used to determine therapeutic effects in living animals. The drugs were administered systemically after predetermination of their blood levels to ensure bioavailability at an appropriate dose level. Whereas compounds selective for a single prostanoid receptor typically exhibited modest but statistically significant inhibition, AGN 211377 profoundly inhibited S-antigen-induced uveitis and laser-induced retinal neovascularization. Consistent with previous polypharmacological studies on chemokine/cytokine release from human macrophages, the prostanoid EP 1 receptor played a permissive role in suppressing neovascularization and inflammation in vivo Comparing AGN 211377 with a close structural congener lacking EP 1 antagonism (AGN 197727), AGN 197727 was much less active than AGN 211377, but pronounced anti-inflammatory and angiostatic effects were achieved by adding the EP 1 antagonist compound (SC-51322) to AGN 197727 in the systemic dosing regimen. Further, AGN 211377 produced superior anti-inflammatory activity compared with the nonsteroidal anti-inflammatory agent ketorolac. These results indicate the value of using a polypharmacological approach in the design of novel therapeutic agents in preference to compounds targeting a single receptor or enzyme. A compound such as AGN 211377 may represent more effective therapy than COX inhibitors in treating uveitis and ocular diseases where neovascularization is a significant part of the pathology.-Woodward, D. F., Wang, J. W., Ni, M., Bauer, A., Martos, J. L., Carling, R. W., Poloso, N. J. In vivo studies validating multitargeting of prostanoid receptors for achieving superior anti-inflammatory effects., (© FASEB.)

A polypharmacologic approach to prostanoid based anti-inflammatory therapeutics was undertaken in order to exploit both the anti- and proinflammatory properties attributed to the various prostanoid receptors. Multitargeting of selected prostanoid receptors yielded a prototype compound, compound 1 (AGN 211377), that antagonizes prostaglandin D2 receptors (DPs) DP1 (49) and DP2 (558), prostaglandin E2 receptors (EPs) EP1 (266) and EP4 (117), prostaglandin F2α receptor (FP) (61), and thromboxane A2 receptor (TP) (11) while sparing EP2, EP3, and prostaglandin I2 receptors (IPs); Kb values (in nanomoles) are given in parentheses. Compound 1 evoked a pronounced inhibition of cytokine/chemokine secretion from lipopolysaccharide or TNF-α stimulated primary human macrophages. These cytokine/chemokines included cluster of designation 40 receptor (CD40), epithelial-derived neutrophil-activating protein 78 (ENA-78), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), IL-8, IL-18, monocyte chemotactic protein-1 (CCL2) (MCP-1), tissue plasminogen activator inhibitor (PAI-1), and regulated on activation, normal T cell expressed and secreted (RANTES). In contrast, the inhibitory effects of most antagonists selective for a single receptor were modest or absent, and selective EP2 receptor blockade increased cytokine release in some instances. Compound 1 also showed clear superiority to the cyclooxygenase inhibitors diclofenac and rofecoxib. These findings reveal that blockade of multiple prostanoid receptors, with absent antagonism of EP2 and IP, may provide more effective anti-inflammatory activity than global suppression of prostanoid synthesis or highly selective prostanoid receptor blockade. These investigations demonstrate the first working example of prostanoid receptor polypharmacology for potentially safer and more effective anti-inflammatory therapeutics by blocking multiple proinflammatory receptors while sparing those with anti-inflammatory activity., (© FASEB.)

Retailers are strategically positioned to leverage environmental improvement over product supply chains through actions targeted at suppliers and consumers. Informed by scientific evidence on environmental hotspots and control points across 14 priority product groups, and a review of 25 major European retailers' actions, this paper proposes a framework to guide and assess retailer best practice in supply chain environmental improvement. Commonly used product standards and improvement measures are classified into "basic" or "good" levels of environmental protection. A hierarchy of eight Best Environmental Management Practices (BEMPs) is proposed to systematically identify and improve the most environmentally damaging supply chains across retail assortments. Widespread third party environmental certification is the most transparent and verifiable mechanism of improvement but may not be appropriate for some supply chains. The enforcement of retailer-defined environmental requirements, and supplier improvement programmes based on performance benchmarking and dissemination of better management practices, are alternative BEMPs that may be used in combination with third party certification. Facilitating consumer selection of frontrunner ecological products is a lower priority BEMP owing to the well documented limitations of this approach. From available data, the highest current or credible-target sales shares of products improved according to the highest priority BEMP and environmental protection level were used to derive "benchmarks of excellence" for each of the 14 product groups. The assessment framework is demonstrated through application to three retailers., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The discovery of anandamide and 2-arachidonyl glycerol (2-AG) as naturally occurring mammalian endocannabinoids has had important and wide-reaching therapeutic implications. This, to a large extent, ensues from the complexity of endocannabinoid biology. One facet of endocannabinoid biology now receiving increased attention is the cyclo-oxygenase-2 (COX-2) derived oxidation products. Anandamide and 2-AG are oxidized to a range of PG-ethanolamides and PG-glyceryl esters that closely approaches that of the prostaglandins (PGs) formed from arachidonic acid. The pharmacology of these electrochemically neutral PG-ethanolamides (prostamides) and PG-glyceryl esters appears to be unique. No meaningful interaction with natural or recombinant prostanoid receptors is apparent. Nevertheless, in certain cells and tissues, prostamides and PG-glyceryl esters exert potent effects. The recent discovery of selective antagonists for the putative prostamide receptor has been a major advance in further establishing prostamide pharmacology as an entity distinct from prostanoid receptors. Since discovery of the prototype prostamide antagonist (AGN 204396), rapid progress has been made. The latest prostamide antagonists (AGN 211334-6) are 100 times more potent than the prototype and are, therefore, sufficiently active to be used in living animal studies. These compounds will allow a full evaluation of the role of prostamides in health and disease. To date, the only therapeutic application for prostamides is in glaucoma. The prostamide analog, bimatoprost, being the most effective ocular hypotensive drug currently available. Interestingly, PGE(2)-glyceryl ester and its chemically stable analog PGE(2)-serinolamide also lower intraocular pressure in dogs. Nevertheless, the therapeutic future of PGE(2)-glyceryl ester is more likely to reside in inflammation.

Purpose: Despite structural similarity with prostaglandin F(2 alpha), the ocular hypotensive agent bimatoprost (Lumigan; Allergan, Inc., Irvine, CA) shows unique pharmacology in vitro and functional activity in vivo. Unfortunately, the precise mechanisms that underlie bimatoprost's distinctive impact on aqueous humor dynamics are unclear. The purpose of the present study was to investigate the effects of bimatoprost and a novel prostamide-selective antagonist AGN 211334 on human conventional drainage., Methods: Two model systems were used to test the consequences of bimatoprost and/or AGN 211334 treatment on conventional drainage. Human anterior segments in organ culture were perfused at a constant flow rate of 2.5 microL/min while pressure was recorded continuously. After stable baseline facilities were established, segments were treated with drug(s), and pressure was monitored for an additional 3 days. In parallel, the drugs' effects on hydraulic conductivity of human trabecular meshwork (TM) cell monolayers were evaluated. Pharmacological properties of AGN 211334 were characterized in isolated feline iris preparations in organ culture and heterologously expressed G-protein-coupled receptors were examined in vitro., Results: Bimatoprost increased outflow facility by an average of 40% +/- 10% within 48 hours of treatment (n = 10, P < 0.001). Preincubation or coincubation with AGN 211334 significantly blunted bimatoprost's effects by 95% or 43%, respectively. Similar results were obtained in cell culture experiments in which bimatoprost increased hydraulic conductivity of TM cell monolayers by 78% +/- 25%. Pretreatment with AGN 211334 completely blocked bimatoprost's effects, while coincubation decreased its effects on average by 74%. In both models, AGN 211334 alone significantly decreased fluid flux across trabecular tissues and cells., Conclusions: The findings indicate that bimatoprost interacts with a prostamide receptor in the trabecular meshwork to increase outflow facility.

A reduction of the tetracyclic skeleton of sordarins and sordaricins to a cyclopentane ring bearing the pharmacophore functional groups led to new derivatives retaining part of their in vitro and whole-cell activity.