A class of pyrrole derivatives endowed with analgesic/anti-inflammatory activity

We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules.     

Aloin enhances cisplatin antineoplastic activity in B16-F10 melanoma cells by transglutaminase-induced differentiation

Aloin, a natural anthracycline from aloe plant, is a hydroxyanthraquinone derivative shown to have antitumor properties. This study demonstrated that aloin exerted inhibition of cell proliferation, adhesion and invasion abilities of B16-F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced melanoma cell differentiation through the enhancement of melanogenesis and transglutaminase activity. To improve the growth-inhibiting effect of anticancer agents, we found that the combined treatment of cells with aloin and low doses of cisplatin increases the antiproliferative activity of aloin. The results suggest that aloin possesses antineoplastic and antimetastatic properties, exerted likely through the induction of melanoma cell differentiation.     

Landscape context determinants to plant diversity in the permanent meadows of Southern European Alps

In the Southern Alps, the role of landscape context on meadows plant diversity was evaluated using a multi-model information theoretic approach and five competing hypotheses of landscape context factors: habitat quality (H1), matrix quality (H2), habitat change (H3), matrix quality change (H4) and topography-environmental conditions (H5)- measured at three spatial scales (125, 250 and 500 m). Shannon diversity index and species richness represented plant diversity obtained in 34 plots (100 m² size). Landscape context affected plant diversity measures differently. Matrix quality change at larger scale (500 m) was the most supported hypothesis explaining Shannon diversity index, while species richness responded mostly to topography-environmental conditions in the immediate surroundings (125 m). No effects of present-day habitat and matrix quality (H1 and H2) were found. Matrix quality change affected positively Shannon diversity index through an effect of landscape neighbourhood context on farming management practices. Due to the importance of exposure and inclination of slopes, topography-environmental conditions influenced species richness mostly through energy-driven processes and farming management strategies. In terms of scale, matrix quality change was the strongest hypothesis explaining Shannon diversity index at all scales, while the underlying process affecting species richness changed with scale (H5 or H3). Overall, landscape context explained only 25–28 % of the variation in plant diversity, suggesting that landscape management may support biodiversity conservation when comprised in a global strategy including farming practices. In the study area, change in landscape diversity may be a good indicator for Shannon diversity index and south-eastern facing meadows should be preserved.     

Use of dredge islands by a declining European shorebird, the Kentish Plover Charadrius alexandrinus

Colonization of newly created habitats is a challenge for waterbird populations in a changing world. Knowing which habitat characteristics are required by waterbird populations is a research challenge for rational management of the new ecosystems and their aquatic bird populations. Since 1989 intertidal dredge islands have been built in the lagoon of Venice using sediments coming from regular dredging of lagoon channels and inlets. Kentish Plover, a species declining in Europe, readily uses these new sites as soon as they become available. Between 2005 and 2007, 75 dredge islands were surveyed each year and the number of breeding pairs of Kentish Plover estimated. Each year about one-third of available dredge islands was used by Kentish Plover. Between 34 (in 2005) and 131 (in 2007) breeding pairs were found, and possible differences in vegetation and morphological characteristics between occupied and unoccupied sites were investigated. Only age, mean elevation above sea level and extension of bare ground were statistically different; Kentish Plover preferred younger sites, with higher elevation and with larger areas of bare ground. The largest groups of breeding pairs, up to thirty pairs, were found on islands which also supported colonies of Little Terns. In the study period dredged islands supported about 60 % of the total breeding population of the lagoon of Venice and 4–6 % of the estimated Italian population. Along coastal sites where human pressure on beaches is particularly heavy, man made habitats such as dredge islands may become a valuable alternative breeding site for this and other species of conservation concern. Management works aimed at promoting the occurrence of this species at selected dredge islands have been made in the lagoon of Venice.     

Weekly oral alendronate in mevalonate kinase deficiency

Background

Mevalonate kinase deficiency (MKD) is caused by mutations in the MVK gene, encoding the second enzyme of mevalonate pathway, which results in subsequent shortage of downstream compounds, and starts in childhood with febrile attacks, skin, joint, and gastrointestinal symptoms, sometimes induced by vaccinations.

Methods

For a history of early-onset corticosteroid-induced reduction of bone mineral density in a 14-year-old boy with MKD, who also had presented three bone fractures, we administered weekly oral alendronate, a drug widely used in the management of osteoporosis and other high bone turnover diseases, which blocks mevalonate and halts the prenylation process.

Results

All of the patient’s MKD clinical and laboratory abnormalities were resolved after starting alendronate treatment.

Conclusions

This observation appears enigmatic, since alendronate should reinforce the metabolic block characterizing MKD, but is crucial because of the ultimate improvement shown by this patient. The anti-inflammatory properties of bisphosphonates are a new question for debate among physicians across various specialties, and requires further biochemical and clinical investigation.

     

The role of forest residues in the accounting for the global warming potential of bioenergy

Bioenergy makes up a significant portion of the global primary energy pie, and its production from modernized technology is foreseen to substantially increase. The climate neutrality of biogenic CO₂ emissions from bioenergy grown from sustainably managed biomass resource pools has recently been questioned. The temporary change caused in atmospheric CO₂ concentration from biogenic carbon fluxes was found to be largely dependent on the length of biomass rotation period. In this work, we also show the importance of accounting for the unutilized biomass that is left to decompose in the resource pool and how the characterization factor for the climate impact of biogenic CO₂ emissions changes whether residues are removed for bioenergy or not. With the case of Norwegian Spruce biomass grown in Norway, we found that significantly more biogenic CO₂ emissions should be accounted towards contributing to global warming potential when residues are left in the forest. For a 100‐year time horizon, the global warming potential bio factors suggest that between 44 and 62% of carbon‐flux, neutral biogenic CO₂ emissions at the energy conversion plant should be attributed to causing equivalent climate change potential as fossil‐based CO₂ emissions. For a given forest residue extraction scenario, the same factor should be applied to the combustion of any combination of stem and forest residues. Life cycle analysis practitioners should take these impacts into account and similar region/species specific factors should be developed.     

Natriuretic Peptide-Guided Therapy in Chronic Heart Failure: A Meta-Analysis of 2,686 Patients in 12 Randomized Trials

Background

The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF.

Methodology/Principal Findings

MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142) or all-cause hospitalization (OR:0.726; CI:0.609 to 0.964; p = 0.077).

Conclusions/Significance

Use of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity.