The Genotoxicity of Acrylfentanyl,Ocfentanyl and Furanylfentanyl Raises the Concern of Long-Term Consequences

Three fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). Pharmacotoxicological data on these three non-pharmaceutical fentanyl analogues are limited and studies on their genotoxicity are not yet available. Therefore, the aim of the present study was to investigate this property. The ability to induce structural and numerical chromosomal aberrations in human lymphoblastoid TK6 cells was evaluated by employing the flow cytometric protocol of the in vitro mammalian cell micronucleus test. Our study demonstrated the non-genotoxicity of Fentanyl, i.e., the pharmaceutical progenitor of the class, while its illicit non-pharmaceutical analogues were found to be genotoxic. In particular, Acrylfentanyl led to a statistically significant increase in the MNi frequency at the highest concentration tested (75 μM), while Ocfentanyl and Furanylfentnyl each did so at both concentrations tested (150, 200 μM and 25, 50 μM, respectively). The study ended by investigating reactive oxygen species (ROS) induction as a possible mechanism linked to the proved genotoxic effect. The results showed a non-statistically significant increase in ROS levels in the cultures treated with all molecules under study. Overall, the proved genotoxicity raises concern about the possibility of serious long-term consequences.     

Experimental evaluation of quinolinium and isoquinolinium derivatives as corrosion inhibitors of mild steel in 0.5 M H<Subscript>2</Subscript>SO<Subscript>4</Subscript> solution

The 1-methylquinolinium iodide (I) Qui⁺, I^– and 2-methylisoquinolinium iodide isoQui⁺, I^– were investigated as a corrosion inhibitors for mild steel in sulfuric acid using electrochemical impedance spectroscopy and potentiodynamic polarization techniques. The results indicated that the corrosion inhibition efficiency and extent of surface coverage were increased with increase in inhibitors concentrations. Polarization curves revealed that both inhibitors acted as a mixed-type inhibitor. The thermodynamic parameters were evaluated for corrosion inhibition process. The adsorption of both inhibitors on mild steel surface obeyed Langmuir adsorption isotherm.     

Distributed Graph Traversals by Relabelling Systems with Applications

Graph traversals are in the basis of many distributed algorithms. In this paper, we use graph relabelling systems to encode two basic graph traversals which are the broadcast and the convergecast. This encoding allows us to derive formal, modular and simple encoding for many distributed graph algorithms. We illustrate this method by investigating the distributed computation of a breadth-first spanning tree and the distributed computation of a minimum spanning tree. Our formalism allows to focus on the correctness of a distributed algorithm rather than on the implementation and the communication details.     

In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.     

Production of a halotolerant lipase from Halomonas sp. strain C2SS100: Optimization by response-surface methodology and application in detergent formulations

The aim of this work was to optimize the production of a new lipase by a halotolerant bacterial strain Halomonas sp. C2SS100, by means of the response-surface methodology (RSM). The process parameters having the most significant effect on lipase production were identified using the Plackett–Burman screening design-of-experiments. Then, Box–Behnken design was applied to optimize lipase activity and the quadratic regression model of the lipase production was built. Indeed, the lipase yield was increased, and the value obtained experimentally (39 ± 2 U/ml) was very close to the rate predicted by the model (40.3 U/ml). Likewise, optimization of parameters by RSM resulted in 2.78-fold increase in lipase activity. These findings provide the first report on lipase production and optimization by a halotolerant bacterial strain belonging to Halomonas genus. Afterward, the biochemical properties of the produced lipase were studied for apply in oil stains removal. The crude lipase showed a maximum activity at 60°C and at pH ranging from 7 to 10. It displayed an important stability at high temperature, pH, and NaCl. Interestingly, this bacterial lipase exhibited a prominent stability toward some commercial solid and liquid detergents after 30 min of incubation at 50°C. The capability of the crude lipase to eliminate stain was ascertained on polycotton fabric pieces stained with lubricating oil. Whether with the addition of hot water alone or of a commercially available detergent, lipase is able to considerably boost the elimination of oil stains. The actual findings highlight the capacity of Halomonas sp. lipase for energy-efficient biocatalytic application.     

QoS for wireless sensor networks: Enabling service differentiation at the MAC sub-layer using CoSenS

Providing service differentiation in wireless sensor networks while proposing simple and highly scalable solution is a challenging problem. We retain the use of CSMA/CA as access protocol because of its simplicity, versatility and good scalability properties. We developed CoSenS, a Collect then Send burst Scheme, on top of it to address its weaknesses while facilitating the implementation of scheduling policies. In this article, we propose a simple and scalable service differentiation solution; we implement fixed priority and earliest deadline first on top of CoSenS. The simulation analysis shows that our solution self-adapts to the traffic variation and greatly enhances end-to-end delay, reliability and deadline meet ratio for urgent traffic while not degrading best effort traffic compared to IEEE 802.15.4 original protocol and IEEE 802.15.4 implementing these scheduling policies. Additionally, CoSenS is implemented and tested on motes. The real experimentation results validated our simulation analysis.     

In Vivo Bio-Activation of JWH-175 to JWH-018: Pharmacodynamic and Pharmacokinetic Studies in Mice

3-(1-Naphthalenylmethyl)-1-pentyl-1H-indole (JWH-175) is a synthetic cannabinoid illegally marketed for its psychoactive cannabis-like effects. This study aimed to investigate and compare in vitro and in vivo pharmacodynamic activity of JWH-175 with that of 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018), as well as evaluate the in vitro (human liver microsomes) and in vivo (urine and plasma of CD-1 male mice) metabolic profile of JWH-175. In vitro binding studies showed that JWH-175 is a cannabinoid receptor agonist less potent than JWH-018 on mouse and human CB1 and CB2 receptors. In agreement with in vitro data, JWH-175 reduced the fESPS in brain hippocampal slices of mice less effectively than JWH-018. Similarly, in vivo behavioral studies showed that JWH-175 impaired sensorimotor responses, reduced breath rate and motor activity, and increased pain threshold to mechanical stimuli less potently than JWH-018. Metabolic studies demonstrated that JWH-175 is rapidly bioactivated to JWH-018 in mice blood, suggesting that in vivo effects of JWH-175 are also due to JWH-018 formation. The pharmaco-toxicological profile of JWH-175 was characterized for the first time, proving its in vivo bio-activation to the more potent agonist JWH-018. Thus, it highlighted the great importance of investigating the in vivo metabolism of synthetic cannabinoids for both clinical toxicology and forensic purposes.