Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling

This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in animal models of depressive-like behavior and in patients with MDD via preferential tonic block of pathologically hyperactive GluN2D subtypes. Tonic Ca²⁺ currents via GluN2D subtypes regulate the homeostatic availability of synaptic proteins. MDD and depressive behaviors may be determined by reduced homeostatic availability of synaptic proteins, due to upregulated tonic Ca²⁺ currents through GluN2D subtypes. The preferential activity of low-potency NMDAR antagonists for GluN2D subtypes may explain their rapid antidepressant effects in the absence of dissociative side effects.     

Adverse effects of gabapentin and lack of anti-allodynic efficacy of amitriptyline in the streptozotocin model of painful diabetic neuropathy.

Amitriptyline and gabapentin are the primary treatments for painful diabetic neuropathy (PDN), and it is clear that they produce beneficial effects, but there are questions about these treatments that have not been adequately addressed. For example, although there is a growing consensus that the therapeutic effects of amitriptyline in pain patients are independent of its effects on mood, it is not clear that amitriptyline has specific and direct effects on pain. There is also a fairly broad consensus that gabapentin is safe and well tolerated, but the side-effect profile of gabapentin has not been adequately assessed in pain populations. The rat streptozotocin (STZ) model of PDN was used (a) to assess the effects of amitriptyline on objective, quantitative measures of tactile allodynia, a common type of pain in PDN patients, and (b) to assess the side effects of gabapentin using measures of motor/ambulatory and cognitive function. Amitriptyline did not attenuate STZ-induced mechanical allodynia, even after chronic administration of high doses. Gabapentin produced robust anti-allodynic effects but also produced deficits in tests of motor/ambulatory and cognitive functions. The present experiments suggest that the beneficial effects of amitriptyline in PDN may not be a result of anti-allodynic efficacy and that gabapentin produces robust anti-allodynic effects but may also produce significant motor and cognitive deficits even at or near the lowest effective doses. These findings challenge the consensus opinions about these primary treatments for PDN and suggest that their therapeutic and adverse effects should be explored further in pain patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid synthesis of new DNMT inhibitors derivatives of procainamide

DNA methyltransferases (DNMTs) are responsible for DNA methylation, an epigenetic modification involved in gene regulation. Families of conjugates of procainamide, an inhibitor of DNMT1, were conceived and produced by rapid synthetic pathways. Six compounds resulted in potent inhibitors of the murine catalytic Dnmt3A/3L complex and of human DNMT1, at least 50 times greater than that of the parent compounds. The inhibitors showed selectivity for C5 DNA methyltransferases. The cytotoxicity of the inhibitors was validated on two tumour cell lines (DU145 and HCT116) and correlated with the DNMT inhibitory potency. The inhibition potency of procainamide conjugated to phthalimide through alkyl linkers depended on the length of the linker; the dodecane linker was the best.     

Local approach to fracture for cleavage crack arrest prediction

Crack arrest can complement the crack initiation concept to assess integrity of structures. This paper deals with the application of a local approach model derived from the RKR model to predict cleavage crack propagation and arrest in thermal shock experiments performed on pre-cracked discs made of a low alloy bainitic steel. The numerical procedure takes into account dynamic effects and an accurate behavior law for the material. Simulations with a crack speed criterion help the identification of the critical stress criterion. The results show a good prediction of the crack jump when a 3D modeling is used.     

Thermoelectric Material Electroplating: a Historical Review

Electrodeposition has been used for decades to deposit various semiconductors on targeted surfaces. It is a powerful method for growing thin films and/or nanostructures with potential thermoelectric properties. It has a competitive edge over physical processes due to its cost-effective operation and facilities. This paper furnishes an overview of the evolution of research in the area of electrodeposition of thermoelectric compounds as a function of time and shape category (bulk, wire, and film). Selected results on V₂VI₃ compounds are organized in a synthetic presentation according to shape. Up-to-date literature coverage is provided, based on over 200 papers and proceedings. In this context, our research group is involved in complementary aspects concerning tailoring electrodeposited film morphology in order to enhance thermoelectric properties. Examples are given dealing with pulse electroplating and nanowires.     

Influence of the hydrophilic-lipophilic balance of sunscreen emulsions on their water resistance property

The use of sunscreens with sun protective cloths is the photoprotection way mostly used by Occidentals. During sweating or a bath, those products should be still efficient. As the emulsion is the mostly used type of product format, it is essential that the scientist knows how to formulate an emulsion which will be water resistant. The HLB (hydrophilic-lipophilic balance) of a formulation has high influence on this characteristic.     

In vitro Leishmanicidal and Trypanosomicidal Properties of Imidazole-Containing Azine and Benzoazine Derivatives

Leishmaniasis and Chagas diseases are two of the most important parasitic diseases in the world. Both belong to the category of Neglected Tropical Diseases, and they cannot be prevented by vaccination. Their treatments are founded in outdated drugs that possess many pernicious side-effects and they're not easy to administer. With the aim of discovering new compounds that could serve as anti-trypanosomal drugs, an antiparasitic study of a synthetic compound family has been conducted. A series of new 1,4-bis(alkylamino)- and 1-alkylamino-4-chloroazine and benzoazine derivatives 1 – 4 containing imidazole rings have been synthesized and identified. Their structures showed a possible interest based on previous work. Their in vitro anti-Leishmania infantum, anti-L. braziliensis, anti-L. donovani and anti-T. cruzi activity were tested, as well as the inhibition of Fe-SOD enzymes. It was found that some of them exhibited quite relevant values indicative of being worthy of future more detailed studies, as most of them showed activity to more than only one parasite species, especially compound 3 c was active for the three studied Leishmania species and also for T. cruzi, which is a very interesting trait as it covers a wide spectrum.     

Electroleaching and electrodeposition of zinc in a single-cell process for the treatment of solid waste

This work deals with zinc beneficiation of industrial solid waste by an electrochemical technique combining electroleaching and electrodeposition in a single-cell process. This technique is based on leaching of the solid waste by the protons generated at the anode and migration of the resulting ions toward the cathode where deposition takes place. A laboratory cell was built for testing the method. It consisted of three compartments, two electrode compartments and a solid waste chamber placed between these. Catholyte and anolyte were sulphuric/sulphate solutions at optimised concentrations. Experiments were first carried out using a zinc solution and an inert matrix in the central compartment, then using a synthetic waste prepared by dispersing zinc oxide in silicon dioxide. Best performance was obtained with treatment duration of 6h, at 4.5Adm(-2) and with catholyte circulation. In this case, a 97% of zinc oxide lixiviation and 75% of zinc-plated were achieved.