The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets

Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders.     

A general framework to study the price‐color relationship in paintings with an application to Mark Rothko rectangular series

We propose a general framework to study the relationship between the price of a painting and its color‐related attributes. To this end we focus on four key aspects: dominant colors, features of the color palette, color harmony, and color emotions. We demonstrate the usefulness of this approach with an example based on Mark Rothko's post‐1950 paintings (the “rectangular” series), and auction data from the 1994 to 2018 period. We identify two distinct price‐color regimes in Rothko's market: (a) [1994‐2005], a period in which prices are explained mainly by the growing popularity of the artist regardless of the color attributes of the paintings sold; and (b) [2006‐2018], a period in which color‐related attributes explain most of the prices. Furthermore, we find that in this second period, the dominant colors and the diversity of the color palette, are by far the most relevant attributes that influence the price; color harmony and color emotions hold almost no explanatory power during this period. Finally, we propose a new metric based on the Herfindahl Index to describe color diversity; this metric seems to be promising at characterizing the effect of the color palette on the price of a painting.     

Sensitivity of Viscosity on Molten Ti Infusion into a B4C-Packed Bed at the Microscale

Metallurgical and Materials Transactions B - The effect of the surface tension–viscosity dissipation driving liquid Ti flow into a B4C packed bed was analyzed at 1941 K and 2573 K. The model...     

Statistical design of sustainable composites from poly(lactic acid) and grape pomace

Biocomposites from poly(lactic acid) (PLA) and grape pomace (GP) were created via injection molding to examine the effects of GP in a PLA matrix. To optimize the mechanical performance the biocomposites were compatibilized with maleic anhydride grafted PLA (MA-g-PLA). The objective of this work was to create a model that could accurately predict the mechanical properties of GP/PLA biocomposites. A region of feasibility for the biocomposites was determined using a statistical design of experiments. Linear regression was used to model the mechanical performance and predicted results with an error of 10% for both tensile and flexural strength and 16% for impact strength. The model was verified with a biocomposite of PLA/GP/MA-g-PLA with a ratio of 62/36/2. This biocomposite had a tensile strength, flexural modulus, and impact strength of 25.8 MPa, 40.0 MPa, and 18.4 J/m, respectively. It was found that a linear model can accurately predict the mechanical properties of PLA/GP/MA-g-PLA biocomposites.     

Phenylvinilbisquinolines as fluorescent markers in functionalized polypropylene films

Polymer Bulletin - In this work, polypropylene films (PP) and maleic anhydride graft polypropylene (PPgMA) at different concentrations of a photoluminescent dye 2,2′-(1,4-phenylenedivinylene)...     

Color evolution during a coating process of pharmaceutical tablet cores by random spraying

Placebo white tablet cores (lactose anhydrous [47.6%], corn starch [23.8%], microcrystalline cellulose [19.1%], polyvinylpyrrolidone [7.9%], magnesium stearate [0.8%], and talcum powder [0.8%]) were coated with a colorant (hydroxypropyl methylcellulose [8% w/v], titanium dioxide [0.2% w/v], FD&C yellow No. 6 with aluminum lacquer [0.8% w/v], polyethylene glycol 4000 [0.4% w/v], and purified water [q.s.p. 100 mL]) using a random spraying method during 130 minutes. During the coating process, batches of 21 samples were extracted every 10 minutes and measured with a DigiEye imaging system. The initial cores showed very similar and uniform colors (Mean Color Difference from the Mean [MCDM] of 0.8 CIELAB units), but partially coated tablets showed lower uniformity (MCDM below 2.0 CIELAB units). There was a high color variability (MCDM about 4.0 CIELAB units) among tablets of the same batch in the period between 10 and 30 minutes, which decreased as the coating process progressed, until achieving a final acceptable value (MCDM below 2.0 CIELAB units). During the coating process, L^* decreased, C^*_ab strongly increased, and h _ab remained nearly constant (disregarding results at 0 and 10 minutes). CIELAB and CIEDE2000 color differences (mainly chroma differences) with respect to the initial color of the tablets were modeled as a function of time by exponential functions with three coefficients. The color change in the interval from 90 to 130 minutes (4.3 CIELAB units, or 2.6 CIEDE2000 units), may be considered negligible bearing in mind the color variability in the batches of 21 samples and typical values of visual color thresholds.     

Characterisation,storage viabilit,and application of microspheres with Lactobacillus paracasei obtained by the extrusion technique

The objective of this study was to evaluate the influence of pH, bile salts and different storage conditions at two different temperatures (30 and 4 °C) on the viability of free and microencapsulated Lactobacillus paracasei. Microspheres encapsulating L. paracasei were obtained using an extrusion method. The efficiency was 87.6%, the diameter 70 µm and the zeta potential 7.22 ± 0.05 mV. Encapsulated L. paracasei showed higher resistance to stomach pH and bile salts compared to free cells. Microspheres were evaluated under four different storage conditions: fresh, suspended in a solution with a pH of 4, suspended in saline solution and lyophilised. The lyophilised microspheres presented the highest stability with 89.2% survival rate after six weeks of storage; however, free bacteria in saline solution (0.145 N) presented a 65.3% survival rate. Finally, a new product (a strawberry ice popsicle) with possible functional characteristics was obtained using microencapsulated L. paracasei.     

Developing an Irreversible Inhibitor of Human DDAH‐1, an Enzyme Upregulated in Melanoma

Inhibitors of the human enzyme dimethylarginine dimethylaminohydrolase‐1 (DDAH‐1) can raise endogenous levels of asymmetric dimethylarginine (ADMA) and lead to a subsequent inhibition of nitric oxide synthesis. In this study, N⁵‐(1‐imino‐2‐chloroethyl)‐L ‐ornithine (Cl‐NIO) is shown to be a potent time‐ and concentration‐dependent inhibitor of purified human DDAH‐1 (K_I=1.3±0.6 μM ; k_inact=0.34±0.07 min^?1), with >500‐fold selectivity against two arginine‐handling enzymes in the same pathway. An activity probe is used to measure the “in cell” IC₅₀ value (6.6±0.2 μM ) for Cl‐NIO inhibition of DDAH‐1 artificially expressed within cultured HEK293T cells. A screen of diverse melanoma cell lines reveals that a striking 50/64 (78 %) of melanoma lines tested showed increased levels of DDAH‐1 relative to normal melanocyte control lines. Treatment of the melanoma A375 cell line with Cl‐NIO shows a subsequent decrease in cellular nitric oxide production. Cl‐NIO is a promising tool for the study of methylarginine‐mediated nitric oxide control and a potential therapeutic lead compound for other indications with elevated nitric oxide production, such as septic shock and idiopathic pulmonary fibrosis.