A family of kojic acid derivatives aimed to remediation of Pb2+ and Cd2+

The present work analyzes the complex formation ability towards Pb2+ and Cd2+ of a series of kojic acid derivatives that join the chelating properties of the pyrone molecules and those of polyamines, with the aim of evaluating how the different effects of oxygen and nitrogen coordinating groups act on the stability of metal complexes. Experimental research is carried out using potentiometric and spectrophotometric techniques supported by 1H and 13C NMR spectroscopy and DFT calculations. Actually, a different coordination mechanism toward Pb2+ and Cd2+ was proved: in the case of Pb2+, coordination takes place exclusively via the oxygen atoms, while the contribute of the nitrogen atoms appears relevant in the case of Cd2+. Lead complexes of all the studied ligands are characterized by significantly stronger stability than those of cadmium. Finally, on the basis of the measured complex formation stabilities, some of the proposed molecules seems promising effective ligands for lead and cadmium ion decorporation from polluted soils or waste waters

Role of nucleus accumbens μ opioid receptors in the effects of morphine on ERK1/2 phosphorylation

Rationale: Despite the critical role attributed to phosphorylated extracellular signal regulated kinase (pERK1/2) in the nucleus accumbens (Acb) in the actions of addictive drugs, the effects of morphine on ERK1/2 phosphorylation in this area are still controversial. Objectives: In order to investigate further this issue, we studied (1) the ability of morphine to affect ERK1/2 phosphorylation in the shell (AcbSh) and core (AcbC) of Sprague-Dawley and Wistar rats and of CD-1 and C57BL/6J mice and (2) the role of dopamine D1 and μ-opioid receptors in Sprague-Dawley rats and CD-1 mice. Methods: The pERK1/2 expression was assessed by immunohistochemistry. Results: In rats, morphine decreased AcbSh and AcbC pERK1/2 expression, whereas in mice, increased it preferentially in the AcbSh compared with the AcbC. Systemic SCH 39166 decreased pERK1/2 expression on its own in the AcbSh and AcbC of Sprague-Dawley rats and CD-1 mice; furthermore, in rats, SCH 39166 disclosed the ability of morphine to stimulate pERK1/2 expression. Systemic (rats and mice) and intra-Acb (rats) naltrexone prevented both decreases, in rats, and increases, in mice. Conclusions: These findings confirm the differential effects of morphine in rats and mice Acb and that D1 receptors exert a facilitatory role on ERK1/2 phosphorylation; furthermore, they indicate that, in rats, removal of the D1-dependent pERK1/2 expression discloses the stimulatory influence of morphine on ERK1/2 phosphorylation and that the morphine’s ability to decrease pERK1/2 expression is mediated by Acb μ-opioid receptors. Future experiments may disentangle the psychopharmacological significance of the effects of morphine on pERK1/2 in the Acb

New perspective for an old drug: Can naloxone be considered an antioxidant agent?

Background: Experimental evidence indicates that Naloxone (NLX) holds antioxidant properties. The present study aims at verifying the hypothesis that NLX could prevent oxidative stress induced by hydrogen peroxide (H2O2) in PC12 cells.Methods: To investigate the antioxidant effect of NLX, initially, we performed electrochemical experiments by means of platinum-based sensors in a cell-free system. Subsequently, NLX was tested in PC12 cells on H2O2induced overproduction of intracellular levels of reactive-oxygen-species (ROS), apoptosis, modification of cells' cycle distribution and damage of cells' plasma membrane.Results: This study reveals that NLX counteracts intracellular ROS production, reduces H2O2-induced apoptosis levels, and prevents the oxidative damage-dependent increases of the percentage of cells in G2/M phase. Likewise, NLX protects PC12 cells from H2O2- induced oxidative damage, by preventing the lactate dehydrogenase (LDH) release. Moreover, electrochemical experiments confirmed the antioxidant properties of NLX.Conclusion: Overall, these findings provide a starting point for studying further the protective effects of NLX on oxidative stress

Simultaneous wireless and high-resolution detection of nucleus accumbens shell ethanol concentrations and free motion of rats upon voluntary ethanol intake

Highly sensitive detection of ethanol concentrations in discrete brain regions of rats voluntarily accessing ethanol, with high temporal resolution, would represent a source of greatly desirable data in studies devoted to understanding the kinetics of the neurobiological basis of ethanol's ability to impact behavior. In the present study, we present a series of experiments aiming to validate and apply an original high-tech implantable device, consisting of the coupling, for the first time, of an amperometric biosensor for brain ethanol detection, with a sensor for detecting the microvibrations of the animal. This device allows the real-time comparison between the ethanol intake, its cerebral concentrations, and their effect on the motion when the animal is in the condition of voluntary drinking. To this end, we assessed in vitro the efficiency of three different biosensor designs loading diverse alcohol oxidase enzymes (AOx) obtained from three different AOx-donor strains: Hansenula polymorpha, Candida boidinii, and Pichia pastoris. In vitro data disclosed that the devices loading H. polymorpha and C. boidinii were similarly efficient (respectively, linear region slope [LRS]: 1.98 ± 0.07 and 1.38 ± 0.04 nA/mM) but significantly less than the P. pastoris-loaded one (LRS: 7.57 ± 0.12 nA/mM). The in vivo results indicate that this last biosensor design detected the rise of ethanol in the nucleus accumbens shell (AcbSh) after 15 minutes of voluntary 10% ethanol solution intake. At the same time, the microvibration sensor detected a significant increase in the rat's motion signal. Notably, both the biosensor and microvibration sensor described similar and parallel time-dependent U-shaped curves, thus providing a highly sensitive and time-locked high-resolution detection of the neurochemical and behavioral kinetics upon voluntary ethanol intake. The results overall indicate that such a dual telemetry unit represents a powerful device which, implanted in different brain areas, may boost further investigations on the neurobiological mechanisms that underlie ethanol-induced motor activity and reward

Synthesis and CNS activities of pyridopyrazinone and pyridodiazepinone derivatives

New tricyclic derivatives with cyclocondensed pyrido-pyrazine 7,10 and pyrido-diazepine 20a,20b skeletons were synthetized and biologically investigated. The compounds, preliminarily tested on explorative, muscle relaxing, antinociceptive, spontaneous motor activities and influence on the narcotic effect of Evipan, revealed interesting CNS depressant and analgesic activities. The pyrido[2,3-e]pyrrolo[1,2-a]pyrazine structure of 7 appeared the most promising for analgesic and neuroleptic activities. The above compounds were assayed also for their capacity to inhibit DNA synthesis in Ehrlich ascites tumor cells; 20a appeared to be able of inducing a significant inhibition

Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one

The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe3+, studied by a combination of chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed us to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe3+. The pFe3+ value 22.0 of P1–iron complexes is noticeably higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al3+, Cu2+ and Zn2+ has been studied to evalu- ate the possible use of P1 against a second toxic metal ion (Al3+), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelato

Steam sauna and mother roasting in Lao PDR: practices and chemical constituents of essential oils of plant species used in postpartum recovery

<p>Abstract</p> <p>Background</p> <p>Fundamental in traditional postpartum recovery in Lao PDR is the use of hotbeds, mother roasting, steam sauna and steam baths. During these treatments medicinal plants play a crucial role, but little has been published about how the treatments are carried out precisely, which species are used, the medicinal properties of these species, and the medicinal efficacy of their chemical constituents.</p> <p>Methods</p> <p>Sixty-five interviews, in 15 rural villages, with women of 4 different ethnic groups were conducted to survey confinement rituals, and postpartum plant use and salience. Essential oils from the main species used were extracted using steam distillation and the main chemical constituents characterized using gas chromatography-mass spectrometry (GC-MS).</p> <p>Results</p> <p>A total of 10 different species were used by three or more of the ethnic groups included in this study. All species were used in steam sauna and bath, but only 3 species were used in hotbed and mother roasting. Essential oils of <it>Amomum villosum, Amomum microcarpum </it>and <it>Blumea balsamifera </it>were found to contain significant amounts of the following terpenes: β-pinene, camphor, bornyl acetate, borneol, linalool, D-limonene, fenchone, terpinen-4-ol and α-terpinene.</p> <p>Conclusions</p> <p>Many of these terpenes have documented antimicrobial and analgesic properties, and some have also synergistic interactions with other terpenes. The mode of application in hotbed and mother roasting differs from the documented mechanisms of action of these terpenes. Plants in these two practices are likely to serve mainly hygienic purposes, by segregating the mother from infection sources such as beds, mats, stools, cloth and towels. Steam sauna medicinal plant use through inhalation of essential oils vapors can possibly have medicinal efficacy, but is unlikely to alleviate the ailments commonly encountered during postpartum convalescence. Steam sauna medicinal plant use through dermal condensation of essential oils, and steam bath cleansing of the perineal area is possibly a pragmatic use of the reported medicinal plants, as terpene constituents have documented antimicrobial, analgesic and anti-inflammatory properties.</p

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation