Formamidines with antinociceptive and antiinflammatory activities

Pursuing our investigations on 7-amino-2,3-polymethyleneindole derivatives, a set of 7-(dimethylaminomethylene)-amino-2,3-polymethyleneindoles, together with some other aryl or cycloalkyl substituted formamidines, were prepared and tested for analgesic and antiinflammatory activities. Several compounds resulted endowed with one or both of these activities; the indole derivatives 1 and 2 exhibited a good degree of both of them

CQE in OWL 2 QL: A "Longest Honeymoon" Approach (extended version)

Controlled Query Evaluation (CQE) has been recently studied in the context of Semantic Web ontologies. The goal of CQE is concealing some query answers so as to prevent external users from inferring confidential information. In general, there exist multiple, mutually incomparable ways of concealing answers, and previous CQE approaches choose in advance which answers are visible and which are not. In this paper, instead, we study a dynamic CQE method, namely, we propose to alter the answer to the current query based on the evaluation of previous ones. We aim at a system that, besides being able to protect confidential data, is maximally cooperative, which intuitively means that it answers affirmatively to as many queries as possible; it achieves this goal by delaying answer modifications as much as possible. We also show that the behavior we get cannot be intensionally simulated through a static approach, independent of query history. Interestingly, for OWL 2 QL ontologies and policy expressed through denials, query evaluation under our semantics is first-order rewritable, and thus in AC0 in data complexity. This paves the way for the development of practical algorithms, which we also preliminarily discuss in the paper.Comment: This paper is the extended version of "P.Bonatti, G.Cima, D.Lembo, L.Marconi, R.Rosati, L.Sauro, and D.F.Savo. Controlled query evaluation in OWL 2 QL: A "Longest Honeymoon" approach" accepted for publication at ISWC 202

Risks of Using Antifouling Biocides in Aquaculture

Biocides are chemical substances that can deter or kill the microorganisms responsible for biofouling. The rapid expansion of the aquaculture industry is having a significant impact on the marine ecosystems. As the industry expands, it requires the use of more drugs, disinfectants and antifoulant compounds (biocides) to eliminate the microorganisms in the aquaculture facilities. The use of biocides in the aquatic environment, however, has proved to be harmful as it has toxic effects on the marine environment. Organic booster biocides were recently introduced as alternatives to the organotin compounds found in antifouling products after restrictions were imposed on the use of tributyltin (TBT). The replacement products are generally based on copper metal oxides and organic biocides. The biocides that are most commonly used in antifouling paints include chlorothalonil, dichlofluanid, DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, Sea-nine 211®), Diuron, Irgarol 1051, TCMS pyridine (2,3,3,6-tetrachloro-4-methylsulfonyl pyridine), zinc pyrithione and Zineb. There are two types of risks associated with the use of biocides in aquaculture: (i) predators and humans may ingest the fish and shellfish that have accumulated in these contaminants and (ii) the development of antibiotic resistance in bacteria. This paper provides an overview of the effects of antifouling (AF) biocides on aquatic organisms. It also provides some insights into the effects and risks of these compounds on non-target organisms

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Characterization and detection of inauthentic coordinated behaviours in strategic information operations on Twitter

In this work there is an analysis based on historical inauthentic Information Operations (IOs) detected by Twitter and removed from the social, used as a ground truth, to study patterns of inauthentic and harmful coordination and to compare them with a dataset of Twitter messages recovered using the Twitter APIs and based on the most used hashtags in the selected IOs. These can be considered authentic and harmless, because surely they don’t come from users involved in the campaign, banned by Twitter. From the archive, the selected IOs come from Honduras and United Arab Emirates (UAE), which used different information strategies. The first was focused only on political aspects and is based on retweets; the second concerned both political and religious contents and exploited classic conversations. First of all highly coordinated communities (HCCs) are extracted from the whole datasets, composed by the union of authentic and inauthentic tweets, to analyze indexes and behaviours and to see if communities of banned users are isolated from the others. Then, some classifiers are applied to each single user of the datasets. The final purpose is to try to predict through supervised machine learning if users are involved in an inauthentic information operation or not, with high precision score

Analgesic properties of N-terminal substituted phenylalanyl-alanine.

Phenylalanylalanine, an in vitro inhibitor of enkephalinase, and some of its N alpha-derivatives are shown to possess an analgesic action when injected i.p. and i.c.v. into mice in the presence or absence of Leu5-enkephalin. In the second case a synergistic response is observed. The intensity of the analgesic response depends markedly on the nature of the N-terminal substituent which affects the hydrophobic character of the resulting dipeptide, its subsequent transport and probably its rate of biotransformation by cleaving enzymes

Basic benzanilides with local anaesthetic activity

Four groups of three isomers structurally related to lidocaine through the vinilogy principle are described and their pharmacological properties evaluated. The new products were obtained introducing an aromatic ring between carbamidic and N-disubstituted aminomethyl groups of the glycinamide chain. This modification allowed the basic group may be located alternatively in the ortho, meta, and para position of the aromatic ring. The ortho isomers were more toxic than the other ones. The evaluation of the local anesthetic potency through surface, infiltration and conduction tests has shown a strict activity-toxicity correlation in each group of isomers. Finally their different potency has been related to the vinilogy principle and to the receptor model of local anaesthetics

Antinociceptive effect of some carboxypeptidase A inhibitors in comparison with D-phenylalanine.

It had previously been shown that D-phenylalanine and hydrocinnamic acid, two in vitro inhibitors of carboxypeptidase A, possess an analgesic action when injected i.p. in mice. We have studied the in vivo effects of indole-3-acetic acid, another carboxypeptidase A inhibitor, and of the following analogs of D-phenylalanine substituted in position 4: D-tyrosine, p-fluoro-D-phenylalanine and trifluoroacetyl-p-fluoro-D-phenylalanine. Whereas indole-3-acetic acid caused a higher and shorter analgesia in comparison with D-phenylalanine, p-fluoro-D-phenylalanine and its N-trifluoroacetyl derivative yielded both a greater and a much longer lasting analgesic effect. Since the latter compound showed only slight inhibitory activity on carboxypeptidase A in vitro, we suggest that inhibition of this enzyme and analgesia might not be directly correlated

'Non-narcotic' analgesia in the mouse by transcutaneous electrical stimulation

The authors, after mentioning the conditions upon which the actual distinction between 'non-narcotic' and 'narcotic' analgesia is based, report the results of experimental research conducted in the mouse in order to establish the position of transcutaneous electrical stimulation (TES) among the different mechanisms having an analgesic action. On the basis of their results by indirect tests (naloxone-test), they state that TES can be included among the analgesic techniques with a 'non-narcotic' effect